Polyphenols for the Treatment of Ischemic Stroke: New Applications and Insights

Ischemic stroke (IS) is a leading cause of death and disability worldwide. Currently, the main therapeutic strategy involves the use of intravenous thrombolysis to restore cerebral blood flow to prevent the transition of the penumbra to the infarct core. However, due to various limitations and complications, including the narrow time window in which this approach is effective, less than 10% of patients benefit from such therapy. Thus, there is an urgent need for alternative therapeutic strategies, with neuroprotection against the ischemic cascade response after IS being one of the most promising options. In the past few decades, polyphenolic compounds have shown great potential in animal models of IS because of their high biocompatibility and ability to target multiple ischemic cascade signaling pathways, although low bioavailability is an issue that limits the applications of several polyphenols. Here, we review the pathophysiological changes following cerebral ischemia and summarize the research progress regarding the applications of polyphenolic compounds in the treatment of IS over the past 5 years. Furthermore, we discuss several potential strategies for improving the bioavailability of polyphenolic compounds as well as some essential issues that remain to be addressed for the translation of the related therapies to the clinic.     

Phenolic Acids and Flavonoids in Acetonic Extract from Quince (Cydonia oblonga Mill.): Nutraceuticals with Antioxidant and Anti-Inflammatory Potential

Quince (Cydonia oblonga Mill.) is a potential source of polyphenolic compounds related with beneficial biological processes. In this study polyphenols from quince fruit were extracted with aqueous acetone at different ratios. A polyphenol profile was identified and quantified by LC-ESI-QqQ. The antioxidant capacity (ORAC and DPPH) and anti-inflammatory effect (inhibition of COX-2 cyclooxygenase) were evaluated in vitro. The results indicated an effect of the aqueous acetone ratio on the extraction of polyphenolic compounds. The higher extraction yields of polyphenolic compounds were attained with 60–75% aqueous acetone. However, extracts obtained with 85% aqueous acetone promoted higher antioxidant and anti-inflammatory effects. Optimal scaling analysis indicated that hydroxycinnamic acids (quinic and chlorogenic), hydroxybenzoic acids (vanillic and syringic), flavonoids (quercetin and kaempferol), dihydrochalcones (neohesperidin) and flavones (acacetin) are related to the antioxidant activity of quince. While phenolic acids, flavonols (kaempferol-3-O-glucoside and rutin) and flavanols (epicatechin) generated the anti-inflammatory effect by inhibiting 52.3% of the COX-2 enzyme. Therefore, a selective extraction of phenolic mix can reduce oxidative stress or inflammatory processes. This suggests the use of quince as a natural source with significant nutraceutical potential.     

From Prebiotic Chemistry to Supramolecular Biomedical Materials: Exploring the Properties of Self-Assembling Nucleobase-Containing Peptides

Peptides and their synthetic analogs are a class of molecules with enormous relevance as therapeutics for their ability to interact with biomacromolecules like nucleic acids and proteins, potentially interfering with biological pathways often involved in the onset and progression of pathologies of high social impact. Nucleobase-bearing peptides (nucleopeptides) and pseudopeptides (PNAs) offer further interesting possibilities related to their nucleobase-decorated nature for diagnostic and therapeutic applications, thanks to their reported ability to target complementary DNA and RNA strands. In addition, these chimeric compounds are endowed with intriguing self-assembling properties, which are at the heart of their investigation as self-replicating materials in prebiotic chemistry, as well as their application as constituents of innovative drug delivery systems and, more generally, as novel nanomaterials to be employed in biomedicine. Herein we describe the properties of nucleopeptides, PNAs and related supramolecular systems, and summarize some of the most relevant applications of these systems.     

Polyphenols and Their Effects on Muscle Atrophy and Muscle Health

Skeletal muscle atrophy is the decrease in muscle mass and strength caused by reduced protein synthesis/accelerated protein degradation. Various conditions, such as denervation, disuse, aging, chronic diseases, heart disease, obstructive lung disease, diabetes, renal failure, AIDS, sepsis, cancer, and steroidal medications, can cause muscle atrophy. Mechanistically, inflammation, oxidative stress, and mitochondrial dysfunction are among the major contributors to muscle atrophy, by modulating signaling pathways that regulate muscle homeostasis. To prevent muscle catabolism and enhance muscle anabolism, several natural and synthetic compounds have been investigated. Recently, polyphenols (i.e., natural phytochemicals) have received extensive attention regarding their effect on muscle atrophy because of their potent antioxidant and anti-inflammatory properties. Numerous in vitro and in vivo studies have reported polyphenols as strongly effective bioactive molecules that attenuate muscle atrophy and enhance muscle health. This review describes polyphenols as promising bioactive molecules that impede muscle atrophy induced by various proatrophic factors. The effects of each class/subclass of polyphenolic compounds regarding protection against the muscle disorders induced by various pathological/physiological factors are summarized in tabular form and discussed. Although considerable variations in antiatrophic potencies and mechanisms were observed among structurally diverse polyphenolic compounds, they are vital factors to be considered in muscle atrophy prevention strategies.     

Research Progress of Antioxidant Nanomaterials for Acute Pancreatitis

Acute pancreatitis (AP) is a complex inflammatory disease caused by multiple etiologies, the pathogenesis of which has not been fully elucidated. Oxidative stress is important for the regulation of inflammation-related signaling pathways, the recruitment of inflammatory cells, the release of inflammatory factors, and other processes, and plays a key role in the occurrence and development of AP. In recent years, antioxidant therapy that suppresses oxidative stress by scavenging reactive oxygen species has become a research highlight of AP. However, traditional antioxidant drugs have problems such as poor drug stability and low delivery efficiency, which limit their clinical translation and applications. Nanomaterials bring a brand-new opportunity for the antioxidant treatment of AP. This review focuses on the multiple advantages of nanomaterials, including small size, good stability, high permeability, and long retention effect, which can be used not only as effective carriers of traditional antioxidant drugs but also directly as antioxidants. In this review, after first discussing the association between oxidative stress and AP, we focused on summarizing the literature related to antioxidant nanomaterials for the treatment of AP and highlighting the effects of these nanomaterials on the indicators related to oxidative stress in pathological states, aiming to provide references for follow-up research and promote clinical application.     

Pharmaceutical Applications of Ionic Liquids: A Personal Account

Ionic liquids (ILs) have been extensively used in drug formulation and delivery as designer solvents and other components because of their inherent tunability and useful physicochemical and biopharmaceutical properties. ILs can be used to manage some of the operational and functional challenges of drug delivery, including drug solubility, permeability, formulation instability, and in vivo systemic toxicity, that are associated with conventional organic solvents/agents. Furthermore, ILs have been recognized as potential solvents to address the polymorphism, limited solubility, poor permeability, instability, and low bioavailability of crystalline drugs. In this account, we discuss the technological progress and strategies toward designing biocompatible ILs and explore potential biomedical applications, namely the solubilization of small and macromolecular drugs, the creation of active pharmaceutical ingredients, and the delivery of pharmaceuticals.     

Thermosensitive acetylated carboxymethyl chitosan gel depot systems sustained release caffeic acid phenethyl ester for periodontitis treatment

Periodontitis is a chronic inflammatory disease of tooth support tissues leading to progressive destruction of periodontal soft tissues as well as alveolar bone, and can be treated with anti-inflammatory and bone-protective agents to prevent disease progression. Caffeic acid phenethyl ester (CAPE) is a natural polyphenolic compound with anti-inflammation, anti-oxidation and bone tissue repair efficacy. In this work, we synthesized a thermosensitive hydrogel matrix of acetylated carboxymethyl chitosan (A-CC), and firstly applied for periodontal local drug delivery. The biocompatible CAPE-loaded A-CC hydrogel (CAPE-A-CC) has the advantages of forming a drug depot in situ, sustained release and precisely improving the drug concentration in the lesion sites compared with traditional systemic administration. In addition, CAPE-A-CC could significantly inhibit the expression of inflammatory cytokines of TNF-α, IL-1β, IL-6, and IL-17 in macrophages, and increased the expression of alkaline phosphatase (ALP) in human periodontal ligament stem cells (hPDLSC) related to osteogenesis. This study develops a novel in situ thermosensitive hydrogel delivery system to improve the therapeutic potential of natural active ingredient for periodontitis therapy.     

Grapevine as a Rich Source of Polyphenolic Compounds

Grapes are rich in primary and secondary metabolites. Among the secondary metabolites, polyphenolic compounds are the most abundant in grape berries. Besides their important impacts on grape and wine quality, this class of compounds has beneficial effects on human health. Due to their antioxidant activity, polyphenols and phenolic acids can act as anti-inflammatory and anticancerogenic agents, and can modulate the immune system. In grape berries, polyphenols and phenolic acids can be located in the pericarp and seeds, but distribution differs considerably among these tissues. Although some classes of polyphenols and phenolic acids are under strict genetic control, the final content is highly influenced by environmental factors, such as climate, soil, vineyard, and management. This review aims to present the main classes of polyphenolic compounds and phenolic acids in different berry tissues and grape varieties and special emphasis on their beneficial effect on human health.     

The role of asbestos morphology on their cellular toxicity: an in vitro 3D Raman/Rayleigh imaging study

Amphiboles caused cohorts of deaths in exposed workers, leading to some of the largest class actions in the industry. Once inhaled, these inorganic fibers are thought to be both chemically and morphologically toxic, and their biopersistence in the lungs over decades lead to progressive pathologies, mesothelioma, and asbestosis. However, this exceptionally long chronicity for human pathologies suggests that chemical toxicity is certainly low, suggesting that morphological parameters could be more relevant in the pathology. Here, we developed a 3D Raman/optical imaging methodology in vitro to characterize both morphological and chemical parameters of cell/fiber interactions. We determined that lung cells could vesiculate amphiboles with length below 5 μm or could embed those not exceeding 15 μm in their fibrous extracellular matrix. Lung cells can thus develop defense strategies for handling the biopersistence of inorganic species, which may thus have major impact for biosafety issues related to nanomaterials.     

Oligonol inhibits UVB-induced COX-2 expression in HR-1 hairless mouse skin--AP-1 and C/EBP as potential upstream targets

Oxidative stress and inflammatory tissue damage are two major events frequently implicated in carcinogenesis. Numerous polyphenolic compounds derived from plants possess antioxidant and anti-inflammatory activities and are hence effective in preventing cancer. Oligonol is a polyphenol formulation enriched with catechin-type oligomers. As an initial approach to assess the chemopreventive potential of oligonol, we have determined its effects on inflammatory as well as oxidative damage in mouse skin irradiated with UVB. Topical application of oligonol onto the dorsal skin of male HR-1 hairless mice 30 min prior to UVB exposure diminished epidermal hyperplasia and formation of 4-hydroxynonenal, a biochemical hallmark of lipid peroxidation. Topical application of oligonol also significantly inhibited UVB-induced cyclooxygenase (COX-2) expression in mouse skin. Oligonol diminished the DNA binding of activator protein-1 (AP-1) and CCAAT/enhancer binding protein (C/EBP), and the expression of C/EBPdelta in mouse skin exposed to UVB. Our study also revealed that oligonol attenuated UVB-induced catalytic activity as well as expression of p38 mitogen-activated protein (MAP) kinase. Moreover, UVB-induced phosphorylation of another upstream kinase Akt was attenuated by oligonol. Taken together, oligonol showed antioxidative and anti-inflammatory effects in UVB-irradiated mouse skin by inhibiting COX-2 expression via blockade of the activation of AP-1 and C/EBP, and upstream kinases including p38 MAP kinase and Akt.     

Coumarin Derivatives in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a non-communicable disease characterized by a chronic inflammatory process of the gut and categorized into Crohn’s disease and ulcerative colitis, both currently without definitive pharmacological treatment and cure. The unclear etiology of IBD is a limiting factor for the development of new drugs and explains the high frequency of refractory patients to current drugs, which are also related to various adverse effects, mainly after long-term use. Dissatisfaction with current therapies has promoted an increased interest in new pharmacological approaches using natural products. Coumarins comprise a large class of natural phenolic compounds found in fungi, bacteria, and plants. Coumarin and its derivatives have been reported as antioxidant and anti-inflammatory compounds, potentially useful as complementary therapy of the IBD. These compounds produce protective effects in intestinal inflammation through different mechanisms and signaling pathways, mainly modulating immune and inflammatory responses, and protecting against oxidative stress, a central factor for IBD development. In this review, we described the main coumarin derivatives reported as intestinal anti-inflammatory products and its available pharmacodynamic data that support the protective effects of these products in the acute and subchronic phase of intestinal inflammation.     

Anti-Inflammatory and Antioxidant Properties of Carvacrol and Magnolol,in Periodontal Disease and Diabetes Mellitus

Periodontal disease and diabetes mellitus are two pathologies that are extremely widespread worldwide and share the feature of chronic inflammation. Carvacrol is a phenolic monoterpenoid, produced by a variety of herbs, the most well-known of which is Origanum vulgare. Magnolol is a traditional polyphenolic compound isolated from the stem bark of Magnolia officinalis, mainly used in Chinese medicine. The purpose of this paper is to review the therapeutic properties of these bioactive compounds, in the treatment of periodontitis and diabetes. Based on our search strategy we conducted a literature search in the PubMed and Google Scholar databases to identify studies. A total of one hundred eighty-four papers were included in the current review. The results show that carvacrol and magnolol have anti-inflammatory, antioxidant, antimicrobial, anti-osteoclastic, and anti-diabetic properties that benefit both pathologies. Knowledge of the multiple activities of carvacrol and magnolol can assist with the development of new treatment strategies, and the design of clinical animal and human trials will maximize the potential benefits of these extracts in subjects suffering from periodontitis or diabetes.     

Fisetin as a Senotherapeutic Agent: Biopharmaceutical Properties and Crosstalk between Cell Senescence and Neuroprotection

Like other organs, brain functions diminish with age. Furthermore, for a variety of neurological disorders—including Alzheimer’s disease—age is one of the higher-risk factors. Since in many Western countries the average age is increasing, determining approaches for decreasing the effects of aging on brain function is taking on a new urgency. Neuroinflammation and oxidative stress are two convoluted key factors in brain aging and chronic neurodegenerative diseases. The diverseness of factors, causing an age-related decrease in brain functions, requires identifying small molecules that have multiple biological activities that can affect all these factors. One great source of these small molecules is related to polyphenolic flavonoids. Recently, 3,3′,4′,7-tetrahydroxyflavone (fisetin) has been reported as a potent senotherapeutic capable of extending lifespan by reducing peroxidation levels and enhancing antioxidant cell responses. The neuroprotective effects of fisetin have been shown in several in vitro and in vivo models of neurological disorders due to its actions on multiple pathways associated with different neurological disorders. The present work aims to collect the most recent achievements related to the antioxidant and neuroprotective effects of fisetin. Moreover, in silico pharmacokinetics, pharmacodynamics, and toxicity of fisetin are also comprehensively described along with emerging novel drug delivery strategies for the amelioration of this flavonol bioavailability and chemical stability.     

Ultrasound‐Activated Sensitizers and Applications

Modalities for photo‐triggered anticancer therapy are usually limited by their low penetrative depth. Sonotheranostics especially sonodynamic therapy (SDT), which is different from photodynamic therapy (PDT) by the use of highly penetrating acoustic waves to activate a class of sound‐responsive materials called sonosensitizers, has gained significant interest in recent years. The effect of SDT is closely related to the structural and physicochemical properties of the sonosensitizers, which has led to the development of new sound‐activated materials as sonosensitizers for various biomedical applications. This Review provides a summary and discussion of the types of novel sonosensitizers developed in the last few years and outlines their specific designs and the potential challenges. The applications of sonosensitizers with various functions such as for imaging and drug delivery as well as in combination with other treatment modalities would provide new strategies for disease therapy.     

Combined use of pharmacophoric models together with drug metabolism and genotoxicity “in silico” studies in the hit finding process

In this study we propose a virtual screening strategy based on the generation of a pharmacophore hypothesis, followed by an in silico evaluation of some ADME-TOX properties with the aim to apply it to the hit finding process and, specifically, to characterize new chemical entities with potential to control inflammatory processes mediated by T lymphocytes such as multiple sclerosis, systemic lupus erithematosus or rheumatoid arthritis. As a result, three compounds with completely novel scaffolds were selected as final hits for future hit-to-lead optimization due to their anti-inflammatory profile. The biological results showed that the selected compounds increased the intracellular cAMP levels and inhibited cell proliferation in T lymphocytes. Moreover, two of these compounds were able to increase the production of IL-4, an immunoregulatory cytokine involved in the selective deviation of T helper (Th) immune response Th type 2 (Th2), which has been proved to have anti-inflammatory properties in several animal models for autoimmune pathologies as multiple sclerosis or rheumatoid arthritis. Thus our pharmacological strategy has shown to be useful to find molecules with biological activity to control immune responses involved in many inflammatory disorders. Such promising data suggested that this in silico strategy might be useful as hit finding process for future drug development.     

The role of crown ethers in drug delivery

The unique structure of the crown ethers has attracted the attention of many scientists to the use of these compounds in organic synthesis, and drug delivery. In recent years, extensive research has been conducted on the use of crown ethers in the drug delivery process. In the drug delivery process, the use of compounds that can act selectively is very important. Crown ethers with their unique structure can appear in various roles in drug delivery. In recent years, the use of crown ethers in the formulation of nano-drugs have attracted the attention of many researchers, and it shows that crown ethers have a great potential in the process of drug delivery. In fact, chemistry plays a role as a medium for transferring information from suitable compounds to drug delivery. Reviewing the results of the research provides the opportunity to create new ideas for using crown ether in new drug delivery systems.     

Point Defect Engineering Boosting the Thermoelectric Properties of Layered 122 Zintl Compounds

The layered 122 Zintl compounds have become an intriguing class of thermoelectric materials due to the promising electronic transport properties and inherently low thermal conductivity, showing the typical characteristics of "phonon-glass electron-crystal". Owing to the unprecedented performance tunability, the thermoelectric properties of the layered-structure compounds are completive with some traditional thermoelectric materials. Point defects involving vacancy, aliovalent doping and equivalent alloying atoms have been introduced to further enhance the thermoelectric properties. This review emphasizes the effects of various point defects on the thermoelectric parameters, and provides perspective on the strategies for increasing the thermoelectric figure of merit zT, which are believed to be applicable for improving the thermoelectric properties of many other compounds.     

The role of the low density lipoprotein receptor pathway in the delivery of lipophilic photosensitizers in the photodynamic therapy of tumours

Lipoproteins are now recognized as major blood carriers of many hydrophobic porphyrins and related chromophores which are being investigated as possible photosensitizers in the photodynamic therapy of tumours. In vitro and in vivo studies have demonstrated the role of the low density lipoprotein (LDL) receptor pathway in the delivery of photosensitizers to tumour cells and its importance in porphyrin accumulation by tumours. Lysosomes, which are involved in the cellular processing of LDL, are important intracellular targets in the LDL-porphyrin-induced phototoxicity. The use of the LDL receptor pathway as a tool for enhancing the selectivity of photosensitizer delivery to tumour cells appears to be a promising field of research in the photodynamic therapy of tumours.     

Emulsions in Health Care Applications—An Overview

Pharmaceutical applications of emulsions are reviewed with special emphasis on the main reasons these vehicles are used and on their limitations. The development of current applications and future directions are considered according to their delivery routes: these routes can be either parenteral, ocular, or oral, or even transdermal. We examine the raw materials generally used in the formulation of these emulsions, and we consider the main factors influencing the release and absorption of the drugs from these vehicles. We also treat the pharmaceutical applications of emulsified vehicles, particularly submicron emulsions, multiple emulsions, and microemulsions. We have also developed some interesting applications of these formulations such as self-emulsifying drug delivery systems, fat emulsions, and drug carrier systems.     

脂质纳米颗粒的制备及在基因治疗中的应用

基因治疗已经成为人类治疗疾病的一种重要手段.然而,为了将基因药物用于临床,需要更加复杂的递送系统.脂质纳米颗粒(LNPs)系统是目前领先的非病毒递送系统,在治疗诊断学方面取得了许多令人鼓舞的进展,其具有实现基因药物临床治疗应用的潜力.由于LNPs纳米尺寸的优势及类脂化合物的生物相容性和生物降解性,LNPs能够克服阻碍基...