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Nutrients May 2024Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate,... (Review)
Review
Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate, prompting a growing demand for novel, safe, and effective therapies. Natural products (NPs) have emerged as promising candidates in drug development due to their diverse biological activities, low toxicity, and minimal side effects. This paper begins by reviewing existing treatment methods and drugs for liver cancer. It then summarizes the therapeutic effects of NPs sourced from various origins on liver cancer. Finally, we analyze the potential mechanisms of NPs in treating liver cancer, including inhibition of angiogenesis, migration, and invasion; regulation of the cell cycle; induction of apoptosis, autophagy, pyroptosis, and ferroptosis; influence on tumor metabolism; immune regulation; regulation of intestinal function; and regulation of key signaling pathways. This systematic review aims to provide a comprehensive overview of NPs research in liver cancer treatment, offering a foundation for further development and application in pharmaceuticals and functional foods.
Topics: Humans; Biological Products; Liver Neoplasms; Apoptosis; Signal Transduction; Antineoplastic Agents; Animals; Antineoplastic Agents, Phytogenic; Autophagy
PubMed: 38892575
DOI: 10.3390/nu16111642 -
Phytomedicine : International Journal... Jul 2024Respiratory diseases pose a grave threat to human life. Therefore, understanding their pathogenesis and therapeutic strategy is important. Ferroptosis is a novel type of... (Review)
Review
BACKGROUND
Respiratory diseases pose a grave threat to human life. Therefore, understanding their pathogenesis and therapeutic strategy is important. Ferroptosis is a novel type of iron-dependent programmed cell death, distinct from apoptosis, necroptosis, and autophagy, characterised by iron, reactive oxygen species, and lipid peroxide accumulation, as well as glutathione (GSH) depletion and GSH peroxidase 4 (GPX4) inactivation. A close association between ferroptosis and the onset and progression of respiratory diseases, including chronic obstructive pulmonary disease, acute lung injury, bronchial asthma, pulmonary fibrosis, and lung cancer, has been reported. Recent studies have shown that traditional Chinese medicine (TCM) compounds exhibit unique advantages in the treatment of respiratory diseases owing to their natural properties and potential efficacy. These compounds can effectively regulate ferroptosis by modulating several key signalling pathways such as system Xc -GSH-GPX4, NCOA4-mediated ferritinophagy, Nrf2-GPX4, and Nrf2/HO-1, thus playing a positive role in improving respiratory diseases.
PURPOSE
This comprehensive review systematically outlines the regulatory role of ferroptosis in the onset and progression of respiratory diseases and provides evidence for treating respiratory diseases by targeting ferroptosis with TCM compounds. These insights aim to offer potential remedies for the clinical prevention and treatment of respiratory diseases.
STUDY DESIGN AND METHODS
We searched scientific databases PubMed, Web of Science, Scopus, and CNKI using keywords such as "ferroptosis","respiratory diseases","chronic obstructive pulmonary disease","bronchial asthma","acute lung injury","pulmonary fibrosis","lung cancer","traditional Chinese medicine","traditional Chinese medicine compound","monomer", and "natural product" to retrieve studies on the therapeutic potential of TCM compounds in ameliorating respiratory diseases by targeting ferroptosis. The retrieved data followed PRISMA criteria (preferred reporting items for systematic review).
RESULTS
TCM compounds possess unique advantages in treating respiratory diseases, stemming from their natural origins and proven clinical effectiveness. TCM compounds can exert therapeutic effects on respiratory diseases by regulating ferroptosis, which mainly involves modulation of pathways such as system Xc -GSH-GPX4,NCOA4-mediated ferritinophagy, Nrf2-GPX4, and Nrf2/HO-1.
CONCLUSION
TCM compounds have demonstrated promising potential in improving respiratory diseases through the regulation of ferroptosis. The identification of specific TCM-related inducers and inhibitors of ferroptosis holds great significance in developing more effective strategies. However, current research remains confined to animal and cellular studies, emphasizing the imperative for further verifications through high-quality clinical data.
Topics: Ferroptosis; Humans; Drugs, Chinese Herbal; Animals; Signal Transduction; Acute Lung Injury; Medicine, Chinese Traditional; Respiratory Tract Diseases; Reactive Oxygen Species; Pulmonary Fibrosis
PubMed: 38824825
DOI: 10.1016/j.phymed.2024.155738 -
Frontiers in Neurology 2024Traumatic brain injury (TBI), a leading cause of high morbidity and mortality, represents a significant global public health challenge. Currently, no effective treatment...
BACKGROUND AND AIM
Traumatic brain injury (TBI), a leading cause of high morbidity and mortality, represents a significant global public health challenge. Currently, no effective treatment for TBI exists. Curcumin, an active compound extracted from the root of , has demonstrated neuroprotective properties both and . Notably, it has shown potential in reducing oxidative stress and inflammation and enhancing redox balance. This paper conducts a systematic review and meta-analysis to explore curcumin's role in TBI animal models extensively. The findings offer valuable insights for future human clinical trials evaluating curcumin as a therapeutic supplement or nutraceutical in TBI management.
METHODS
Comprehensive literature searches were conducted across MEDLINE, Embase, Cochrane, Web of Science, and Google Scholar databases. These searches aimed to identify relevant manuscripts in all languages, utilizing the keywords "curcumin" and "traumatic brain injury."
RESULTS
The final quantitative analysis included 18 eligible articles corresponding to animal studies. The analysis revealed that curcumin significantly reduced inflammatory cytokines, including IL-1β ( = 0.000), IL-6 ( = 0.002), and TNF-α ( = 0.000), across various concentrations, time points, and administration routes. Additionally, curcumin markedly enhanced the activity of oxidative stress markers such as SOD ( = 0.000), Sir2 ( = 0.000), GPx ( = 0.000), and Nrf2 ( = 0.000), while reducing MDA ( = 0.000), 4-HNE ( = 0.001), and oxyprotein levels ( = 0.024). Furthermore, curcumin improved cerebral edema ( = 0.000) and upregulated neuroprotective factors like synapsin I ( = 0.019), BDNF ( = 0.000), and CREB ( = 0.000), without reducing mNSS ( = 0.144). About autophagy and apoptosis, curcumin increased the activity of Beclin-1 ( = 0.000) and Bcl-2 ( = 0.000), while decreasing caspase-3 ( = 0.000), the apoptosis index ( = 0.000), and P62 ( = 0.002).
CONCLUSION
Curcumin supplementation positively affects traumatic brain injury (TBI) by alleviating oxidative stress and inflammatory responses and promoting neuroprotection. It holds potential as a therapeutic agent for human TBI. However, this conclusion necessitates further substantiation through high-quality literature and additional randomized controlled trials (RCTs).
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/. The registration number of PROSPERO: CRD42023452685.
PubMed: 38798711
DOI: 10.3389/fneur.2024.1380353 -
Biomedicine & Pharmacotherapy =... Jul 2024Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising... (Review)
Review
Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising human life and health. Activating transcription factor 4 (ATF4) participates in the regulation of multiple pathophysiological processes, including CNS disorders. Considering the widespread involvement of ATF4 in the pathological process of CNS disorders, the targeted regulation of ATF4 by plant-derived bioactive compounds (PDBCs) may become a viable strategy for the treatment of CNS disorders. However, the regulatory relationship between PDBCs and ATF4 remains incompletely understood. Here, we aimed to comprehensively review the studies on PDBCs targeting ATF4 to ameliorate CNS disorders, thereby offering novel directions and insights for the treatment of CNS disorders. A computerized search was conducted on PubMed, Embase, Web of Science, and Google Scholar databases to identify preclinical experiments related to PDBCs targeting ATF4 for the treatment of CNS disorders. The search timeframe was from the inception of the databases to December 2023. Two assessors conducted searches using the keywords "ATF4," "Central Nervous System," "Neurological," "Alzheimer's disease," "Parkinson's Disease," "Stroke," "Spinal Cord Injury," "Glioblastoma," "Traumatic Brain Injury," and "Spinal Cord Injury." Overall, 31 studies were included, encompassing assessments of 27 PDBCs. Combining results from in vivo and in vitro studies, we observed that these PDBCs, via ATF4 modulation, prevent the deposition of amyloid-like fibers such as Aβ, tau, and α-synuclein. They regulate ERS, reduce the release of inflammatory factors, restore mitochondrial membrane integrity to prevent oxidative stress, regulate synaptic plasticity, modulate autophagy, and engage anti-apoptotic mechanisms. Consequently, they exert neuroprotective effects in CNS disorders. Numerous PDBCs targeting ATF4 have shown potential in facilitating the restoration of CNS functionality, thereby presenting expansive prospects for the treatment of such disorders. However, future endeavors necessitate high-quality, large-scale, and comprehensive preclinical and clinical studies to further validate this therapeutic potential.
Topics: Activating Transcription Factor 4; Humans; Central Nervous System Diseases; Animals; Phytochemicals; Neuroprotective Agents
PubMed: 38795641
DOI: 10.1016/j.biopha.2024.116811 -
Journal of Clinical Medicine May 2024: Although osteoarthritis (OA) development is epidemiologically multifactorial, a primary underlying mechanism is still under debate. Understanding the pathophysiology... (Review)
Review
: Although osteoarthritis (OA) development is epidemiologically multifactorial, a primary underlying mechanism is still under debate. Understanding the pathophysiology of OA remains challenging. Recently, experts have focused on autophagy as a contributor to OA development. : To better understand the pathogenesis of OA, we survey the literature on the role of autophagy and the molecular mechanisms of OA development. To identify relevant studies, we used controlled vocabulary and free text keywords to search the MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, and SCOPUS database. Thirty-one studies were included for data extraction and systematic review. Among these studies, twenty-five studies investigated the effects of autophagy in aging and OA chondrocytes, six studies examined the effects of autophagy in normal human chondrocytes, and only one study investigated the effects of mechanical stress-induced autophagy on the development of OA in normal chondrocytes. : The studies suggest that autophagy activation prevents OA by exerting cell-protective effects in normal human chondrocytes. However, in aging and osteoarthritis (OA) chondrocytes, the role of autophagy is intricate, as certain studies indicate that stimulating autophagy in these cells can have a cytotoxic effect, while others propose that it may have a protective (cytoprotective) effect against damage or degeneration. : Mechanical stress-induced autophagy is also thought to be involved in the development of OA, but further research is required to identify the precise mechanism. Thus, autophagy contributions should be interpreted with caution in aging and the types of OA cartilage.
PubMed: 38792546
DOI: 10.3390/jcm13103005 -
Frontiers in Pharmacology 2024Intracerebral hemorrhage (ICH), a common subtype of hemorrhagic stroke, often causes severe disability or death. ICH induces adverse events that might lead to secondary...
Intracerebral hemorrhage (ICH), a common subtype of hemorrhagic stroke, often causes severe disability or death. ICH induces adverse events that might lead to secondary brain injury (SBI), and there is currently a lack of specific effective treatment strategies. To provide a new direction for SBI treatment post-ICH, the systematic review discussed how thrombin impacts secondary injury after ICH through several potentially deleterious or protective mechanisms. We included 39 studies and evaluated them using SYRCLE's ROB tool. Subsequently, we explored the potential molecular mechanisms of thrombin-mediated effects on SBI post-ICH in terms of inflammation, iron deposition, autophagy, and angiogenesis. Furthermore, we described the effects of thrombin in endothelial cells, astrocytes, pericytes, microglia, and neurons, as well as the harmful and beneficial effects of high and low thrombin concentrations on ICH. Finally, we concluded the current research status of thrombin therapy for ICH, which will provide a basis for the future clinical application of thrombin in the treatment of ICH.
PubMed: 38698822
DOI: 10.3389/fphar.2024.1293428 -
Biomedicine & Pharmacotherapy =... Jun 2024Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new class of glucose-lowering drugs traditionally used to control blood glucose levels in patients with type 2... (Review)
Review
Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new class of glucose-lowering drugs traditionally used to control blood glucose levels in patients with type 2 diabetes mellitus, have been proven to reduce major adverse cardiovascular events, including cardiovascular death, in patients with heart failure irrespective of ejection fraction and independently of the hypoglycemic effect. Because of their favorable effects on the kidney and cardiovascular outcomes, their use has been expanded in all patients with any combination of diabetes mellitus type 2, chronic kidney disease and heart failure. Although mechanisms explaining the effects of these drugs on the cardiovascular system are not well understood, their effectiveness in all these conditions suggests that they act at the intersection of the metabolic, renal and cardiac axes, thus disrupting maladaptive vicious cycles while contrasting direct organ damage. In this systematic review we provide a state of the art of the randomized controlled trials investigating the effect of SGLT2i on cardiovascular outcomes in patients with chronic kidney disease and/or heart failure irrespective of ejection fraction and diabetes. We also discuss the molecular targets and signaling pathways potentially explaining the cardiac effects of these pharmacological agents, from a clinical and experimental perspective.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Animals; Heart Failure; Treatment Outcome; Renal Insufficiency, Chronic; Randomized Controlled Trials as Topic; Blood Glucose
PubMed: 38678962
DOI: 10.1016/j.biopha.2024.116650 -
Frontiers in Aging Neuroscience 2024With the aging of the population, the health of the elderly has become increasingly important. Postoperative cognitive dysfunction (POCD) is a common neurological...
With the aging of the population, the health of the elderly has become increasingly important. Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients following general anesthesia or surgery. It is characterized by cognitive decline that may persist for weeks, months, or even longer. Electroacupuncture (EA), a novel therapy that combines physical nerve stimulation with acupuncture treatment from traditional Chinese medicine, holds potential as a therapeutic intervention for preventing and treating POCD, particularly in elderly patients. Although the beneficial effects of EA on POCD have been explored in preclinical and clinical studies, the reliability of EA is limited by methodological shortcomings, and the underlying mechanisms remain largely unexplored. Therefore, we have synthesized existing evidence and proposed potential biological mechanisms underlying the effects of EA on neuroinflammation, oxidative stress, autophagy, the microbiota-gut-brain axis, and epigenetic modification. This review summarizes recent advances in EA and POCD, provides a theoretical foundation, explores potential molecular mechanisms for the prevention and treatment of POCD, and offers a basis for conducting relevant clinical trials.
PubMed: 38596595
DOI: 10.3389/fnagi.2024.1384075 -
Antioxidants (Basel, Switzerland) Mar 2024Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder that gives rise to motor incoordination and progressive functional disabilities.... (Review)
Review
Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder that gives rise to motor incoordination and progressive functional disabilities. Although pharmacological interventions have revealed promising prospects in the management of SCA3, adverse effects may become unbearable. The use of herbal remedies in traditional Chinese medicine (TCM) may serve as potential alternative medicines to delay the progression of the disease. This systematic review is intended to identify, appraise, and summarize the findings of studies pertaining to the therapeutic roles of herbal remedies in TCM targeting oxidative stress in the management of SCA3. A literature search for relevant articles published from 1 January 2013 to 30 June 2023 in three databases, namely PubMed, Web of Science, and Scopus, was carried out according to the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of ten preclinical studies met the inclusion criteria of the systematic review. We recognized the therapeutic potential of , , sp., , , , , , sp., , , , , and . We identified the types of preclinical models expressing polyglutamine (polyQ) expanded mutant protein (mATXN3), inducers of oxidative stress that mimic the SCA3 pathogenesis, and effective doses of the herbal remedies. The modes of action contributing to the attenuation of oxidative stress are activation of antioxidant pathways, ubiquitin-proteasome system and autophagy, regulation of apoptosis, proinflammatory signaling pathway and chaperones, regulation of mitochondrial function and biogenesis, and restoration of neurotransmission and synaptic plasticity. In conclusion, herbal remedies in TCM may possibly delay the progression of SCA3, therefore providing justification for clinical trials.
PubMed: 38539908
DOI: 10.3390/antiox13030375 -
Antioxidants (Basel, Switzerland) Mar 2024Ferroptosis is a recently discovered type of programmed cell death that is mechanistically different from other types of programmed cell death such as apoptosis,... (Review)
Review
Ferroptosis is a recently discovered type of programmed cell death that is mechanistically different from other types of programmed cell death such as apoptosis, necroptosis, and autophagy. It is characterized by the accumulation of intracellular iron, overproduction of reactive oxygen species, depletion of glutathione, and extensive lipid peroxidation of lipids in the cell membrane. It was discovered that ferroptosis is interconnected with many diseases, such as neurodegenerative diseases, ischemia/reperfusion injury, cancer, and chronic kidney disease. Polyphenols, plant secondary metabolites known for many bioactivities, are being extensively researched in the context of their influence on ferroptosis which resulted in a great number of publications showing the need for a systematic review. In this review, an extensive literature search was performed. Databases (Scopus, Web of Science, PubMed, ScienceDirect, Springer) were searched in the time span from 2017 to November 2023, using the keyword "ferroptosis" alone and in combination with "flavonoid", "phenolic acid", "stilbene", "coumarin", "anthraquinone", and "chalcone"; after the selection of studies, we had 311 papers and 143 phenolic compounds. In total, 53 compounds showed the ability to induce ferroptosis, and 110 compounds were able to inhibit ferroptosis, and out of those compounds, 20 showed both abilities depending on the model system. The most researched compounds are shikonin, curcumin, quercetin, resveratrol, and baicalin. The most common modes of action are in the modulation of the Nrf2/GPX4 and Nrf2/HO-1 axis and the modulation of iron metabolism.
PubMed: 38539867
DOI: 10.3390/antiox13030334