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Phytotherapy Research : PTR Jan 2024Inflammation, a type of the body's defense against injury or infection, causes many chronic disorders including diabetes, cardiovascular disease, and cancer. Therefore,... (Review)
Review
Inflammation, a type of the body's defense against injury or infection, causes many chronic disorders including diabetes, cardiovascular disease, and cancer. Therefore, discovering natural compounds with numerous biological activities for the management of inflammation is highly recommended. Out of natural compounds, peppermint and its main component, menthol, has been suggested to possess antiinflammatory potential. Four databases including Web of Sciences, PubMed, Scopus, and Embase were searched to identify articles about peppermint and its antiinflammatory effects up to March 2023. Out of 3805 records screened, 14 articles met the study criteria. The evidence reviewed here proposed peppermint as an antiinflammatory agent. Peppermint may suppress inflammation by activating the AMP-activated protein kinase/unc-51 like kinase 1/nuclear factor-E2 associated factor 2 autophagy pathway, downregulating extracellular signal-regulated kinase-nuclear factor kappa B and mitogen activated protein kinases pathways, attenuating oxidative stress, suppressing the production of pro-inflammatory mediators and nitric oxide, and inducing the production of antiinflammatory prostaglandins. Due to the promising antiinflammatory effects of peppermint and the lack of human studies in this regard, future randomized clinical trials examining the effects of peppermint on inflammation and its related maladies are warranted.
Topics: Animals; Humans; Mice; Rats; Anti-Inflammatory Agents; Extracellular Signal-Regulated MAP Kinases; Inflammation; Lipopolysaccharides; Mentha piperita; Monocytes; NF-kappa B; Plant Extracts; In Vitro Techniques
PubMed: 37850332
DOI: 10.1002/ptr.8041 -
Heliyon Sep 2023Geniposide, as a pharmacologically bioactive component, is derived from a classic and common Chinese herb, Ellis. Geniposide has been shown to be effective for treating...
Protective effect and possible mechanisms of geniposide for ischemia-reperfusion injury: A systematic review with meta-analysis and network pharmacology of preclinical evidence.
BACKGROUND
Geniposide, as a pharmacologically bioactive component, is derived from a classic and common Chinese herb, Ellis. Geniposide has been shown to be effective for treating I/R injury in recent studies. Current effectively pharmaceutical treatments are scarce, and treatment based on geniposide may become a novel option. As far as we know, this research is the initial systematic evaluation of the protective effects of geniposide in I/R injury.
AIM OF THE STUDY
This study is engrossed in evaluating the mechanism of action of geniposide in I/R injury through a preclinical systematic review with meta-analysis and network pharmacology.
MATERIALS AND METHODS
We built a systematic review which provided a view of effect and mechanism of geniposide for I/R injury. Based on seven databases, an open-ended search from their inception to August 31st, 2022, was conducted. Animal studies on the effects of geniposide in I/R injury were considered. The data was analyzed using Review Manager 5.3, and bias was assessed using the CAMARADES 10-item scale. 13 articles including 279 animals were selected finally. And network pharmacology was joined to elucidate the mechanism.
RESULTS
According to the meta-analysis, in I/R injury, geniposide can attenuate cardiomyocytes viability and the size of MI, decrease the volume of cerebral infraction and neurological score, decrease serum ALT and AST activity, and downregulated serum Cr and BUN. The review found that geniposide protects against I/R injury by inhibiting apoptosis, oxidation, inflammation and improvement of autophagy and mitochondrial respiration, which is consistent with the results of the network pharmacology screening.
CONCLUSION
This preclinical systematic review including meta-analysis and network pharmacology, which was the first one summarizing the relationship between geniposide and ischemia diseases, shows a novel therapy for I/R injury and appears an enticing implication of geniposide in I/R injury, and further research is looked forward. Given the restricted quantity of included researches and the unclear risk of bias of the studies, we should interpret the results with caution.
PubMed: 37809705
DOI: 10.1016/j.heliyon.2023.e20114 -
Frontiers in Immunology 2023Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2... (Review)
Review
Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, emerging as novel hypoglycemic agents, have demonstrated significant cardiorenal protective effects in patients with DKD. Initially, it was believed that the efficacy of SGLT-2 inhibitors declined as the estimated glomerular filtration rate (eGFR) decreased, which led to their preferential use in DKD patients at G1-G3 stages. However, recent findings from the DAPA-CKD and EMPA-KIDNEY studies have revealed equally beneficial cardiorenal effects of SGLT-2 inhibitors in individuals at stage G4 DKD, although the underlying mechanism behind this phenomenon remains unclear. In this comprehensive analysis, we provide a systematic review of the mechanisms and functioning of SGLT-2 inhibitors, potential renal protection mechanisms, and the therapeutic efficacy and safety of SGLT-2 inhibitors in kidney diseases, with a particular focus on stage G4 DKD. Gaining a deeper understanding of the renal protective effect of SGLT-2 inhibitors and their underlying mechanisms is highly significance for the successful utilization of these inhibitors in the treatment of diverse kidney disorders.
Topics: Humans; Sodium-Glucose Transporter 2 Inhibitors; Diabetic Nephropathies; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Kidney
PubMed: 37809091
DOI: 10.3389/fimmu.2023.1213473 -
European Journal of Medicinal Chemistry Dec 2023Targeted protein degradation (TPD) has emerged as a promising therapeutic approach with potential advantages over traditional occupancy-based inhibitors in terms of... (Review)
Review
Targeted protein degradation (TPD) has emerged as a promising therapeutic approach with potential advantages over traditional occupancy-based inhibitors in terms of dosing, side effects and targeting "undruggable" proteins. Targeted degraders can theoretically bind any nook or cranny of targeted proteins to drive degradation. This offers convenience versus the small-molecule inhibitors that must function in a well-defined pocket. The degradation process depends mainly on two cell self-destruction mechanisms, namely the ubiquitin-proteasome system and the lysosomal degradation pathway. Various TPD strategies (e.g., proteolytic-targeting chimeras, molecular glues, lysosome-targeting chimeras, and autophagy-targeting chimeras) have been developed. These approaches hold great potential for targeting dysregulated proteins, potentially offering therapeutic benefits. In this article, we systematically review the mechanisms of various TPD strategies, potential applications to drug discovery, and recent advances. We also discuss the benefits and challenges associated with these TPD strategies, aiming to provide insight into the targeting of dysregulated proteins and facilitate their clinical applications.
Topics: Proteolysis; Proteasome Endopeptidase Complex; Autophagy; Drug Discovery; Lysosomes
PubMed: 37778240
DOI: 10.1016/j.ejmech.2023.115839 -
Indian Journal of Pharmacology 2023Although evidence suggests ginsenosides, the primary active and distinctive components of ginseng, have beneficial effects in cisplatin-induced nephrotoxicity, their... (Meta-Analysis)
Meta-Analysis Review
Although evidence suggests ginsenosides, the primary active and distinctive components of ginseng, have beneficial effects in cisplatin-induced nephrotoxicity, their efficacy and protective mechanisms remain unclear. The aim of the current meta-analysis is to study the effectiveness and mechanisms of ginsenosides in a model of nephrotoxicity induced by cisplatin. Preclinical investigations were conducted in the search of various databases including Medline, Web of Science, Google, CNKI, Embase, and the Wanfang database. 12 studies with 216 animals were included in this review. Stata 15.0 and RevMan 5.3 were used for statistical analyses. The pooled results showed that ginsenosides significantly improved kidney function, and inhibited histological damage. The protective mechanism of ginsenosides is associated with its antioxidative stress, anti-inflammation, anti-apoptosis, and anti-autophagy. The results of our study indicate that ginsenosides have the potential to mitigate nephrotoxicity induced by cisplatin through the modulation of various targets and pathways. Consequently, ginsenosides hold promise as therapeutic agents for the clinical management and prevention of cisplatin-induced nephrotoxicity.
Topics: Animals; Cisplatin; Ginsenosides; Kidney; Oxidative Stress
PubMed: 37737077
DOI: 10.4103/ijp.ijp_251_23 -
Frontiers in Pharmacology 2023To summarize and clarify the current research status and indicate possible future directions in the field of autophagy in ischemic stroke, we performed a comprehensive...
To summarize and clarify the current research status and indicate possible future directions in the field of autophagy in ischemic stroke, we performed a comprehensive and multidimensional bibliometric analysis of the literature in this field published from 2011 to 2022. We retrieved articles on the field of autophagy in ischemic stroke published between 2011 and 2022 from Web of Science Core Collection (WOSCC). VOSviewer (version 1.6.19) and CiteSpace (version 6.2.R2 Basic) were used to identify the leading topics as well as generate visual maps of Countries/regions, organizations, authors, journals, and keyword networks in the related field. A total of 568 publications were contained in this research. The journal with the most publications were Front Pharmacol, Mol Neurobiol, and Neuroscience. China was the most productive country with respect to co-authorship, with the Capital Med Univ being the organization with the most. co-authorships. In terms of authorship analysis, eight of the top 10 most contributive authors were from China. The co-occurring author keywords can be divided into three main clusters, including "protective effect of autophagy in ischemic stroke," "autophagy-targeted therapy for ischemic stroke," and "mitochondrial function in cerebral ischemia-reperfusion injury". This bibliometric analysis helps us reveal the current research hotspots in the research field of autophagy in ischemic stroke and guide future research directions. Subsequent trends in this special field are likely to identify and develop novel autophagy-targeted therapy strategies to effectively prevent and treat ischemic stroke.
PubMed: 37731738
DOI: 10.3389/fphar.2023.1232114 -
Nutritional Neuroscience Sep 2023Spinal cord injury (SCI) is a potentially fatal neurological disease with severe complications and a high disability rate. An increasing number of animal experimental... (Review)
Review
CONTEXT
Spinal cord injury (SCI) is a potentially fatal neurological disease with severe complications and a high disability rate. An increasing number of animal experimental studies support the therapeutic effect of quercetin, which is a natural anti-inflammatory and antioxidant bioflavonoid.
OBJECTIVE
This paper reviewed the therapeutic effect of quercetin on a rat SCI model and summarized the relevant mechanistic research.
DATA SOURCES
PubMed, EMBASE, Web of Science, Science Direct, WanFang Data, SinoMed databases, the China National Knowledge Infrastructure, and the Vip Journal Integration Platform were searched from their inception to April 2023 for animal experiments applying quercetin to treat SCI.
STUDY SELECTION
Based on the PICOS criteria, a total of 18 eligible studies were included, of which 14 were high quality.
RESULTS
In this study, there was a gradual increase in effect based on the Basso, Beattie, and Bresnahan (BBB) score after three days (< 0.0001). Furthermore, gender differences also appeared in the efficacy of quercetin; males performed better than females ( = 0.008). Quercetin was also associated with improved inclined plane test score ( = 0.008). In terms of biochemical indicators, meta-analysis showed that MDA ( < 0.0001) and MPO ( = 0.0002) were significantly reduced after quercetin administration compared with the control group, and SOD levels were increased ( = 0.004). Mechanistically, quercetin facilitates the inhibition of oxidative stress, inflammation, autophagy and apoptosis that occur after SCI.
CONCLUSIONS
Generally, this systematic review suggests that quercetin has a neuroprotective effect on SCI.
PubMed: 37691351
DOI: 10.1080/1028415X.2023.2257425 -
Cell Biology International Nov 2023Breast cancer is a commonly known cancer type and the leading cause of cancer death among females. One of the unresolved problems in cancer treatment is the increased... (Review)
Review
Breast cancer is a commonly known cancer type and the leading cause of cancer death among females. One of the unresolved problems in cancer treatment is the increased resistance of the tumor to existing treatments, which is a direct result of apoptotic defects. Calculating an alternative to cell death (autophagy) may be the ultimate solution to maximizing cancer cell death. Our aim in this study was to investigate the potential of free nanoparticles (un-drug-loaded) in the induction or inhibition of autophagy and consider this effect on the therapy process. When the studies met the inclusion criteria, the full texts of all relevant articles were carefully examined and classified. Of the 25 articles included in the analysis, carried out on MCF-7, MDA-MB-231, MDA-MB-231-TXSA, MDA-MB-468, SUM1315, and 4T1 cell lines. Twenty in vitro studies and five in vivo/in vitro studies applied five different autophagy tests: Acridine orange, western blot, Cyto-ID Autophagy Detection Kit, confocal microscope, and quantitative polymerase chain reaction. Nanoparticles (NPs) in the basic format, including Ag, Au, Y O , Se, ZnO, CuO, Al, Fe, vanadium pentoxide, and liposomes, were prepared in the included articles. Three behaviors of NPs related to autophagy were seen: induction, inhibition, and no action. Screened and presented data suggest that most of the involved free NPs (metallic NPs) in this systematic review had reactive oxygen species-mediated pathways with autophagy induction (36%). Also, PI3K/Akt/mTOR and MAPK/ERK signaling pathways were mentioned in just four studies (16%). An impressive percentage of studies (31%) did not examine the NP-related autophagy pathway.
PubMed: 37671447
DOI: 10.1002/cbin.12081 -
Mutation Research. Reviews in Mutation... 2023The development of resistance by tumor cells to various types of therapy is a significant problem that decreases the effectiveness of oncology treatments. For more than... (Review)
Review
The development of resistance by tumor cells to various types of therapy is a significant problem that decreases the effectiveness of oncology treatments. For more than two decades, comparative transcriptomic studies of tumor cells with different sensitivities to ionizing radiation and chemotherapeutic agents have been conducted in order to identify the causes and mechanisms underlying this phenomenon. However, the results of such studies have little in common and often contradict each other. We have assumed that a systematic analysis of a large number of such studies will provide new knowledge about the mechanisms of development of therapeutic resistance in tumor cells. Our comparison of 123 differentially expressed gene (DEG) lists published in 98 papers suggests a very low degree of consistency between the study results. Grouping the data by type of genotoxic agent and tumor type did not increase the similarity. The most frequently overexpressed genes were found to be those encoding the transport protein ABCB1 and the antiviral defense protein IFITM1. We put forward a hypothesis that the role played by the overexpression of the latter in the development of resistance may be associated not only with the stimulation of proliferation, but also with the limitation of exosomal communication and, as a result, with a decrease in the bystander effect. Among down regulated DEGs, BNIP3 was observed most frequently. The expression of BNIP3, together with BNIP3L, is often suppressed in cells resistant to non-platinum genotoxic chemotherapeutic agents, whereas it is increased in cells resistant to ionizing radiation. These observations are likely to be mediated by the binary effects of these gene products on survival, and regulation of apoptosis and autophagy. The combined data also show that even such obvious mechanisms as inhibition of apoptosis and increase of proliferation are not universal but show multidirectional changes.
Topics: Humans; Gene Expression Profiling; Transcriptome; RNA; Apoptosis; DNA Damage
PubMed: 37657754
DOI: 10.1016/j.mrrev.2023.108467 -
Phytomedicine : International Journal... Nov 2023Verbascoside is a natural and water-soluble phenylethanoid glycoside found in several medicinal plants. It has extensive pharmacological effects, including antioxidative... (Review)
Review
BACKGROUND
Verbascoside is a natural and water-soluble phenylethanoid glycoside found in several medicinal plants. It has extensive pharmacological effects, including antioxidative and antineoplastic actions, and a wide range of therapeutic effects against depression.
PURPOSE
In this review, we appraised preclinical and limited clinical evidence to fully discuss the anti-depression capacity of verbascoside and its holistic characteristics that can contribute to better management of depression in vivo and in vitro models, as well as, its toxicities and medicinal value.
METHODS
This review was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic review of 32 preclinical trials published up to April 2023, combined with a comprehensive bioinformatics analysis of network pharmacology and molecular docking, was conducted to elucidate the antidepressant mechanism of action of verbascoside. Studies included in the systematic review were obtained from 7 electronic databases: PubMed, Scopus, Web of Science, Cochrane, ResearchGate, ScienceDirect, and Google Scholar.
RESULTS
Studies on the antidepressant effects of verbascoside showed that various pharmacological mechanisms and pathways, such as modulating the levels of monoamine neurotransmitters, inhibiting hypothalamic-pituitary-adrenal (HPA) axis hyperfunction and promoting neuroprotection may be involved in the process of its action against depression. Verbascoside promotes dopamine (DA) biosynthesis by promoting the expression of tyrosine hydroxylase mRNA and protein, upregulates the expression of 5-hydroxytryptamine receptor 1B (5-HT1B), prominence protein, microtubule-associated protein 2 (MAP2), hemeoxygenase-1 (HO-1), SQSTM1, Recombinant Autophagy Related Protein 5 (ATG5) and Beclin-1, and decreases the expression of caspase-3 and a-synuclein, thus exerting antidepressant effects. We identified seven targets (CCL2, FOS, GABARAPL1, CA9, TYR, CA12, and SQSTM1) and three signaling pathways (glutathione metabolism, metabolism of xenobiotics by cytochrome P450, fluid shear stress and atherosclerosis) as potential molecular biological sites for verbascoside.
CONCLUSIONS
These findings provide strong evidence that verbascoside exerts its antidepressant effects through various pharmacological mechanisms. However, further multicentre clinical case-control and molecularly targeted fishing studies are required to confirm the clinical efficacy of verbascoside and its underlying direct targets.
Topics: Glycosides; Molecular Docking Simulation; Neuroprotection; Sequestosome-1 Protein
PubMed: 37657207
DOI: 10.1016/j.phymed.2023.155027