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Molecules (Basel, Switzerland) Nov 2023The number of patients with Alzheimer's disease (AD) continues to rise and, despite the efforts of researchers, there are still no effective treatments for this...
The number of patients with Alzheimer's disease (AD) continues to rise and, despite the efforts of researchers, there are still no effective treatments for this multifaceted disease. The main objective of this work was the search for multifunctional and more effective anti-Alzheimer agents. Herein, we report the evaluation of a library of quercetin-1,2,3-triazole hybrids () in antioxidant, hydrogen peroxide-induced oxidative stress protection, and cholinesterases (AChE and BuChE) inhibitory activities. Hybrids and showed potent in vitro inhibitory activity on BuChE (IC values between 11.2 and 65.7 μM). Hybrid , the best inhibitor, was stronger than galantamine, displaying an IC value of 11.2 μM for BuChE, and is also a competitive inhibitor. Moreover, toxicity evaluation for the most promising hybrids was performed using the toxicity assay, showing low toxicity. Hybrids , and did not affect viability at 12.5 μM and also displayed a protective effect against oxidative stress induced by hydrogen peroxide in cell damage in MCF-7 cells. Hybrids , and act as multifunctional ligands in AD pathologies.
Topics: Humans; Cholinesterase Inhibitors; Quercetin; Hydrogen Peroxide; Alzheimer Disease; Galantamine; Acetylcholinesterase; Structure-Activity Relationship; Drug Design; Neuroprotective Agents
PubMed: 38005217
DOI: 10.3390/molecules28227495 -
Animal Models and Experimental Medicine Aug 2023The risk of internal and external exposure to ionizing radiation (IR) has increased alongside the development and implementation of nuclear technology. Therefore,... (Review)
Review
The risk of internal and external exposure to ionizing radiation (IR) has increased alongside the development and implementation of nuclear technology. Therefore, serious security issues have emerged globally, and there has been an increase in the number of studies focusing on radiological prevention and medical countermeasures. Radioprotective drugs are particularly important components of emergency medical preparedness strategies for the clinical management of IR-induced injuries. However, a few drugs have been approved to date to treat such injuries, and the related mechanisms are not entirely understood. Thus, the aim of the present review was to provide a brief overview of the World Health Organization's updated list of essential medicines for 2023 for the proper management of national stockpiles and the treatment of radiological emergencies. This review also discusses the types of radiation-induced health injuries and the related mechanisms, as well as the development of various radioprotective agents, including Chinese herbal medicines, for which significant survival benefits have been demonstrated in animal models of acute radiation syndrome.
Topics: Animals; Acute Radiation Syndrome; Radiation, Ionizing; Civil Defense; Drugs, Essential; Medical Countermeasures; Radiation-Protective Agents
PubMed: 37642199
DOI: 10.1002/ame2.12339 -
Molecular Neurobiology Sep 2023Human life and health are gravely threatened by brain diseases. The onset and progression of the illnesses are influenced by a variety of factors, including pathogenic... (Review)
Review
Human life and health are gravely threatened by brain diseases. The onset and progression of the illnesses are influenced by a variety of factors, including pathogenic causes, environmental factors, mental issues, etc. According to scientific studies, neuroinflammation and oxidative stress play a significant role in the development and incidence of brain diseases by producing pro-inflammatory cytokines and oxidative tissue damage to induce inflammation and apoptosis. Neuroinflammation, oxidative stress, and oxidative stress-related changes are inseparable factors in the etiology of several brain diseases. Numerous neurodegenerative diseases have undergone substantial research into the therapeutic alternatives that target oxidative stress, the function of oxidative stress, and the possible therapeutic use of antioxidants. Formerly, tBHQ is a synthetic phenolic antioxidant, which has been widely used as a food additive. According to recent researches, tBHQ can suppress the processes that lead to neuroinflammation and oxidative stress, which offers a fresh approach to treating brain diseases. In order to achieve the goal of decreasing inflammation and apoptosis, tBHQ is a specialized nuclear factor erythroid 2-related factor (Nrf2) activator that decreases oxidative stress and enhances antioxidant status by upregulating the Nrf2 gene and reducing nuclear factor kappa-B (NF-κB) activity. This article reviews the effects of tBHQ on neuroinflammation and oxidative stress in recent years and looks into how tBHQ inhibits neuroinflammation and oxidative stress through human, animal, and cell experiments to play a neuroprotective role in Alzheimer's disease (AD), stroke, depression, and Parkinson's disease (PD). It is anticipated that this article will be useful as a reference for upcoming research and the creation of drugs to treat brain diseases.
Topics: Animals; Humans; Antioxidants; Neuroprotective Agents; NF-E2-Related Factor 2; Neuroinflammatory Diseases; Oxidative Stress; Hydroquinones; Brain Diseases
PubMed: 37191855
DOI: 10.1007/s12035-023-03370-3 -
Renal Failure Dec 2023Patients with diabetic kidney disease (DKD) are at increased risk to develop post-contrast acute kidney injury (AKI). Diabetic patients under dipeptidyl peptidase 4... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Patients with diabetic kidney disease (DKD) are at increased risk to develop post-contrast acute kidney injury (AKI). Diabetic patients under dipeptidyl peptidase 4 inhibitors (DPP4Is) experience a lower propensity to develop AKI. We speculated that linagliptin as a single agent or in combination with allopurinol may reduce the incidence of post-contrast AKI in stage 3-5 chronic kidney disease (CKD) patients with underlying DKD.
METHODS
Out of 951 DKD patients eligible for this study, 800 accepted to sign informed consent. They were randomly allocated to 4 equal groups that received their prophylaxis for 2 days before and after radiocontrast. The first control group received N-acetyl cysteine and saline, the 2 received allopurinol, the 3 group received linagliptin, and the 4 received both allopurinol and linagliptin. Post-procedure follow-up for kidney functions was conducted for 2 weeks in all patients.
RESULTS
20, 19, 14, and 8 patients developed post-contrast AKI in groups 1 through 4, respectively. Neither linagliptin nor allopurinol was superior to N-acetyl cysteine and saline alone. However, the combination of the two agents provided statistically significant renal protection: post-contrast AKI in group 4 was significantly lower than in groups 1 and 2 ( < 0.02 and <0.03, respectively). None of the post-contrast AKI cases required dialysis.
CONCLUSION
Linagliptin and allopurinol in combination may offer protection against post-contrast AKI in DKD exposed to radiocontrast. Further studies are needed to support this view.
TRIAL REGISTRATION CLINICALTRIALS.GOV
NCT03470454.
Topics: Humans; Acute Kidney Injury; Allopurinol; Diabetic Nephropathies; Kidney Failure, Chronic; Linagliptin; Prospective Studies; Renal Insufficiency, Chronic; Contrast Media; Chemoprevention; Drug Therapy, Combination; Acetylcysteine; Protective Agents; Saline Solution
PubMed: 36974638
DOI: 10.1080/0886022X.2023.2194434 -
Phytomedicine : International Journal... Jun 2024Nobiletin is a natural polymethoxylated flavonoid widely present in citrus fruit peels. It has been demonstrated to exert the effects of anti-tumor, anti-inflammation,... (Review)
Review
BACKGROUND
Nobiletin is a natural polymethoxylated flavonoid widely present in citrus fruit peels. It has been demonstrated to exert the effects of anti-tumor, anti-inflammation, anti-oxidative, anti-apoptotic and improve cardiovascular function. Increasing evidences suggest that nobiletin plays an important role in respiratory diseases (RDs) treatment.
OBJECTIVE
This review aimed to investigate the therapeutic potential of nobiletin against RDs, such as lung cancer, COPD, pulmonary fibrosis, asthma, pulmonary infection, acute lung injury, coronavirus disease 2019, and pulmonary arterial hypertension.
METHODS
We retrieved extensive literature of relevant literatures in English until June 26, 2023 from the database of PubMed, Web of Science, and Scopus databases. The keywords of "nobiletin and lung", "nobiletin and respiratory disease", "nobiletin and chronic respiratory diseases", "nobiletin and metabolites", "nobiletin and pharmacokinetics", "nobiletin and toxicity" were searched in pairs. A total of 298 literatures were retrieved from the above database. After excluding the duplicates and reviews, 53 were included in the current review.
RESULTS
We found that the therapeutic mechanisms are based on different signaling pathways. Firstly, nobiletin inhibited the proliferation and suppressed the invasion and migration of cancer cells by regulating the related pathway or key target, like Bcl-2, PD-L1, PARP, and Akt/GSK3β/β-catenin in lung cancer treatment. Secondly, nobiletin treats COPD and ALI by targeting classical signaling pathway mediating inflammation. Besides, the available findings show that nobiletin exerts the effect of PF treatment via regulating mTOR pathway.
CONCLUSIONS
With the wide range of pharmacological activities, high efficiency and low toxicity, nobiletin can be used as a potential agent for preventing and treating RDs. These findings will contribute to further research on the molecular mechanisms of nobiletin and facilitate in-depth studies on nobiletin at both preclinical and clinical levels for the treatment of RDs.
Topics: Flavones; Humans; Animals; COVID-19 Drug Treatment; COVID-19; Respiratory Tract Diseases; Antioxidants
PubMed: 38522319
DOI: 10.1016/j.phymed.2024.155506 -
Molecular Pharmaceutics Nov 2023Amifostine (AMF, also known as WR-2721) is the only approved broad-spectrum small-molecule radiation protection agent that can combat hematopoietic damage caused by... (Review)
Review
Amifostine (AMF, also known as WR-2721) is the only approved broad-spectrum small-molecule radiation protection agent that can combat hematopoietic damage caused by ionizing radiation and is used as an antitumor adjuvant and cell protector in cancer chemotherapy and radiotherapy. Amifostine is usually injected intravenously before chemotherapy or radiotherapy and has been used in the treatment of head and neck cancer. However, the inconvenient intravenous administration and its toxic side effects such as hypotension have severely limited its further application in clinic. In order to reduce the toxic and side effects, scientists are trying to develop a variety of drug administration methods and are devoted to developing a wide application of amifostine in radiation protection. This paper reviews the research progress of amifostine for radiation protection in recent years, discusses its mechanism of action, clinical application, and other aspects, with focus on summarizing the most widely studied amifostine injection administration and drug delivery systems, and explored the correlation between various administrations and drug efficacies.
Topics: Humans; Amifostine; Radiation Protection; Radiation-Protective Agents; Administration, Intravenous; Adjuvants, Immunologic; Drug-Related Side Effects and Adverse Reactions
PubMed: 37747899
DOI: 10.1021/acs.molpharmaceut.3c00600 -
Journal of Controlled Release :... Jun 2024In recent years, the intersection of the academic and medical domains has increasingly spotlighted the utilization of biomaterials in radioactive disease treatment and... (Review)
Review
In recent years, the intersection of the academic and medical domains has increasingly spotlighted the utilization of biomaterials in radioactive disease treatment and radiation protection. Biomaterials, distinguished from conventional molecular pharmaceuticals, offer a suite of advantages in addressing radiological conditions. These include their superior biological activity, chemical stability, exceptional histocompatibility, and targeted delivery capabilities. This review comprehensively delineates the therapeutic mechanisms employed by various biomaterials in treating radiological afflictions impacting the skin, lungs, gastrointestinal tract, and hematopoietic systems. Significantly, these nanomaterials function not only as efficient drug delivery vehicles but also as protective agents against radiation, mitigating its detrimental effects on the human body. Notably, the strategic amalgamation of specific biomaterials with particular pharmacological agents can lead to a synergistic therapeutic outcome, opening new avenues in the treatment of radiation- induced diseases. However, despite their broad potential applications, the biosafety and clinical efficacy of these biomaterials still require in-depth research and investigation. Ultimately, this review aims to not only bridge the current knowledge gaps in the application of biomaterials for radiation-induced diseases but also to inspire future innovations and research directions in this rapidly evolving field.
Topics: Humans; Biocompatible Materials; Animals; Radiation Injuries; Radiation Protection; Radiation-Protective Agents; Drug Delivery Systems
PubMed: 38692438
DOI: 10.1016/j.jconrel.2024.04.044 -
Bioprocess and Biosystems Engineering Dec 2023Due to recent global warming threats, the changes in the atmosphere have caused significant ultraviolet (UV) radiation exposure, primarily emitted by the sun, which... (Review)
Review
Due to recent global warming threats, the changes in the atmosphere have caused significant ultraviolet (UV) radiation exposure, primarily emitted by the sun, which creates more awareness of photoprotection. Sunscreen development has been a convenient and crucial approach to photoprotection against ultraviolet radiation. Due to high demand, upgrading the quality of sunscreen products and certifying methods are necessary to guarantee the safety of commercial sunscreen products for use. Sunscreen products should have a satisfactory amount of sun protection factor (SPF), ultraviolet A protection factor, as well as the photostability of the sunscreens for them to be considered effective and safe for use. A rigorous study on the effectiveness of the sunscreen components and their safety standards is essential for the productive use and further improvement of the available sunscreen materials. This article summarizes the effects and issues, protective measures of sunscreen usage, and its components, mainly ultraviolet filters.
Topics: Sunscreening Agents; Ultraviolet Rays; Skin
PubMed: 37656257
DOI: 10.1007/s00449-023-02919-9 -
Phytotherapy Research : PTR May 2024As the global population ages, preventing lifestyle- and aging-related diseases is increasing, necessitating the search for safe and affordable therapeutic... (Review)
Review
As the global population ages, preventing lifestyle- and aging-related diseases is increasing, necessitating the search for safe and affordable therapeutic interventions. Among nutraceuticals, quercetin, a flavonoid ubiquitously present in various plants, has garnered considerable interest. This review aimed to collate and analyze existing literature on the therapeutic potentials of quercetin, especially its interactions with SIRTs and its clinical applicability based on its bioavailability and safety. This narrative review was based on a literature survey spanning from 2015 to 2023 using PUBMED. The keywords and MeSH terms used were: "quercetin" AND "bioavailability" OR "metabolism" OR "metabolites" as well as "quercetin" AND "SIRTuin" OR "SIRT*" AND "cellular effects" OR "pathway" OR "signaling" OR "neuroprotective" OR "cardioprotective" OR "nephroprotective" OR "antiatherosclerosis" OR "diabetes" OR "antidiabetic" OR "dyslipidemia" AND "mice" OR "rats". Quercetin demonstrates multiple therapeutic activities, including neuroprotective, cardioprotective, and anti-atherosclerotic effects. Its antioxidant, anti-inflammatory, antiviral, and immunomodulatory properties are well-established. At a molecular level, it majorly interacts with SIRTs, particularly SIRT1 and SIRT6, and modulates numerous signaling pathways, contributing to its therapeutic effects. These pathways play roles in reducing oxidative stress, inflammation, autophagy regulation, mitochondrial biogenesis, glucose utilization, fatty acid oxidation, and genome stability. However, clinical trials on quercetin's effectiveness in humans are scarce. Quercetin exhibits a wide range of SIRT-mediated therapeutic effects. Despite the compelling preclinical data, more standardized clinical trials are needed to fully understand its therapeutic potential. Future research should focus on addressing its bioavailability and safety concerns.
Topics: Quercetin; Humans; Animals; Sirtuins; Antioxidants; Biological Availability; Anti-Inflammatory Agents; Neuroprotective Agents; Oxidative Stress; Sirtuin 1; Signal Transduction
PubMed: 38429891
DOI: 10.1002/ptr.8168 -
Bioorganic & Medicinal Chemistry Letters Aug 2023Naturally occurring homoisoflavonoids have attracted significant attention in the field of medicinal chemistry due to their potential health benefits and diverse range...
Naturally occurring homoisoflavonoids have attracted significant attention in the field of medicinal chemistry due to their potential health benefits and diverse range of biological properties. Recently, C-prenylated homoisoflavonoids, namely ledebourin A, B, and C, were isolated from the bulbs of Ledebouria floribunda and have exhibited potent antioxidant activity. In this study, we successfully synthesized ledebourin A and its regioisomer, compounds 1 and 9. By comparing the NMR spectra of the synthesized compounds with those of reported ledebourin A, we observed discrepancies. Nonetheless, our synthesis and subsequent findings offer valuable insights into the structural revision and biological activities of these unique prenylated homoisoflavonoids. Both synthesized compounds 1 and 9 exhibited no toxicity towards Hep-G2 cells and displayed the ability to recover glyceraldehyde-induced cell death, suggesting their potential as protective agents against liver damage.
Topics: Isoflavones; Antioxidants; Plant Extracts; Magnetic Resonance Spectroscopy; Molecular Structure
PubMed: 37369329
DOI: 10.1016/j.bmcl.2023.129390