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Nutrients Aug 2022The therapeutic effects of food rich in ellagitannins have been established to stem from its microbial metabolite, urolithin. Over the past decade, there has been a... (Review)
Review
UNLABELLED
The therapeutic effects of food rich in ellagitannins have been established to stem from its microbial metabolite, urolithin. Over the past decade, there has been a growing trend in urolithin research pertaining to its pharmacological properties. The purpose of this systematic review is to collate and synthesise all available data on urolithin's therapeutic ability, to highlight its potential as a pharmaceutical agent, and prospective direction on future research.
METHODS
This systematic review was written based on the PRISMA guideline and was conducted across Ovid via Embase, Ovid MEDLINE, Cochrane Central Register for Controlled Trials, and Web of Science Core Collection.
RESULTS
A total of 41 animal studies were included in this systematic review based on the appropriate keyword. The included studies highlighted the neuroprotective, anti-metabolic disorder activity, nephroprotective, myocardial protective, anti-inflammatory, and musculoskeletal protection of urolithin A, B, and its synthetic analogue methylated urolithin A. The Sirt1, AMPK, and PI3K/AKT/mTOR signalling pathways were reported to be involved in the initiation of autophagy and mitochondrial biogenesis by urolithin A.
CONCLUSIONS
This review methodically discusses the therapeutic prospects of urolithins and provides scientific justification for the potential development of urolithin A as a potent natural mitophagy inducer for anti-ageing purposes.
Topics: Animals; Coumarins; Hydrolyzable Tannins; Phosphatidylinositol 3-Kinases; Prospective Studies
PubMed: 36079752
DOI: 10.3390/nu14173494 -
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 2021Natural product-based cancer preventive and therapeutic entities, such as flavonoids and their derivatives, are shown to have a noticeable capability to suppress tumor...
Natural product-based cancer preventive and therapeutic entities, such as flavonoids and their derivatives, are shown to have a noticeable capability to suppress tumor formation and cancer cell growth. Naringin, a natural flavanone glycoside present in various plant species, has been indicated to modulate different signaling pathways and interact with numerous cell signaling molecules, which allows for an extensive variety of pharmacological actions, such as amelioration of inflammation, oxidative stress, metabolic syndromes, bone disorders, and cancer. The purpose of this systematic review is to present a critical and comprehensive assessment of the antitumor ability of naringin and associated molecular targets in various cancers. Studies were identified through systematic searches of Science Direct, PubMed, and Scopus as well as eligibility checks according to predefined selection criteria. Eighty-seven studies were included in this systematic review. There was strong evidence for the association between treatment with naringin alone, or combined with other drugs and antitumor activity. Additionally, studies showed that naringin-metal complexes have greater anticancer effects compared to free naringin. It has been demonstrated that naringin employs multitargeted mechanisms to hamper cancer initiation, promotion, and progression through modulation of several dysregulated signaling cascades implicated in cell proliferation, autophagy, apoptosis, inflammation, angiogenesis, metastasis, and invasion. The results of our work show that naringin is a promising candidate for cancer prevention and treatment, and might offer substantial support for the clinical application of this phytocompound in the future. Nevertheless, further preclinical and clinical studies as well as drug delivery approaches are needed for designing novel formulations of naringin to realize the full potential of this flavonoid in cancer prevention and intervention.
PubMed: 33854437
DOI: 10.3389/fphar.2021.639840 -
Frontiers in Cell and Developmental... 2024Cell death is ubiquitous during development and throughout life and is a genetically determined active and ordered process that plays a crucial role in regulating... (Review)
Review
Cell death is ubiquitous during development and throughout life and is a genetically determined active and ordered process that plays a crucial role in regulating homeostasis. Cell death includes regulated cell death and non-programmed cell death, and the common types of regulatory cell death are necrosis, apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis. Apoptosis, Necrosis and necroptosis are more common than autophagy, ferroptosis and pyroptosis among cell death. Non-coding RNAs are regulatory RNA molecules that do not encode proteins and include mainly microRNAs, long non-coding RNAs, and circular RNAs. Non-coding RNAs can act as oncogenes and tumor suppressor genes, with significant effects on tumor occurrence and development, and they can also regulate tumor cell autophagy, ferroptosis, and pyroptosis at the transcriptional or post-transcriptional level. This paper reviews the recent research progress on the effects of the non-coding RNAs involved in autophagy, ferroptosis, and pyroptosis on tumorigenesis, tumor development, and treatment, and looks forward to the future direction of this field, which will help to elucidate the molecular mechanisms of tumorigenesis and tumor development, as well as provide a new vision for the treatment of tumors.
PubMed: 38481525
DOI: 10.3389/fcell.2024.1284934 -
Frontiers in Cell and Developmental... 2021Cancer cells reprogram glucose metabolism to meet their malignant proliferation needs and survival under a variety of stress conditions. The prominent metabolic...
Cancer cells reprogram glucose metabolism to meet their malignant proliferation needs and survival under a variety of stress conditions. The prominent metabolic reprogram is aerobic glycolysis, which can help cells accumulate precursors for biosynthesis of macromolecules. In addition to glycolysis, recent studies show that gluconeogenesis and TCA cycle play important roles in tumorigenesis. Here, we provide a comprehensive review about the role of glycolysis, gluconeogenesis, and TCA cycle in tumorigenesis with an emphasis on revealing the novel functions of the relevant enzymes and metabolites. These functions include regulation of cell metabolism, gene expression, cell apoptosis and autophagy. We also summarize the effect of glucose metabolism on chromatin modifications and how this relationship leads to cancer development. Understanding the link between cancer cell metabolism and chromatin modifications will help develop more effective cancer treatments.
PubMed: 33987181
DOI: 10.3389/fcell.2021.654337 -
Immunoregulatory framework and the role of miRNA in the pathogenesis of NSCLC - A systematic review.Frontiers in Oncology 2022With a 5-year survival rate of only 15%, non-small cell lung cancer (NSCLC), the most common kind of lung carcinoma and the cause of millions of deaths annually, has... (Review)
Review
With a 5-year survival rate of only 15%, non-small cell lung cancer (NSCLC), the most common kind of lung carcinoma and the cause of millions of deaths annually, has drawn attention. Numerous variables, such as disrupted signaling caused by somatic mutations in the EGFR-mediated RAS/RAF/MAPK, PI3K/AKT, JAK/STAT signaling cascade, supports tumour survival in one way or another. Here, the tumour microenvironment significantly contributes to the development of cancer by thwarting the immune response. MicroRNAs (miRNAs) are critical regulators of gene expression that can function as oncogenes or oncosuppressors. They have a major influence on the occurrence and prognosis of NSCLC. Though, a myriad number of therapies are available and many are being clinically tested, still the drug resistance, its adverse effect and toxicity leading towards fatality cannot be ruled out. In this review, we tried to ascertain the missing links in between perturbed EGFR signaling, miRNAs favouring tumorigenesis and the autophagy mechanism. While connecting all the aforementioned points multiple associations were set, which can be targeted in order to combat NSCLC. Here, we tried illuminating designing synthetically engineered circuits with the toggle switches that might lay a prototype for better therapeutic paradigm.
PubMed: 36620544
DOI: 10.3389/fonc.2022.1089320 -
Journal of Cancer Research and Clinical... Jan 2024Human papilloma virus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) displays distinct epidemiological, clinical, and molecular characteristics compared to... (Review)
Review
PURPOSE
Human papilloma virus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) displays distinct epidemiological, clinical, and molecular characteristics compared to the negative counterpart. Alterations in autophagy play an important role in cancer, and emerging evidence indicates an interplay of autophagy in HNSCC carcinogenesis and tumor promotion. However, the influence of HPV infection on autophagy in HNSCC has received less attention and has not been previously reviewed. Therefore, we here aimed to systematically review the role of autophagy explicitly in HPV HNSCC.
METHODS
Studies accessible in PubMed, Embase, Scopus, and Web of Science investigating HNSCC, highlighting the molecular biological differences between HPV and HPV HNSCC and its influences on autophagy in HNSCC were analyzed according to the PRISMA statement. A total of 10 articles were identified, included, and summarized.
RESULTS
The HPV16 E7 oncoprotein was reported to be involved in the degradation of AMBRA1 and STING, and to enhance chemotherapy-induced cell death via lethal mitophagy in HNSCC cells. Autophagy-associated gene signatures correlated with HPV-subtype and overall survival. Additionally, immunohistochemical (IHC) analyses indicate that high LC3B expression correlates with poor overall survival in oropharyngeal HNSCC patients.
CONCLUSION
HPV may dampen general bulk autophagic flux via degradation of AMBRA1 but may promote selective autophagic degradation of STING and mitochondria. Interpretations of correlations between autophagy-associated gene expressions or IHC analyses of autophagy-related (ATG) proteins in paraffin embedded tissue with clinicopathological features without biological validation need to be taken with caution.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Papillomavirus Infections; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Autophagy; Adaptor Proteins, Signal Transducing
PubMed: 38291202
DOI: 10.1007/s00432-023-05514-3 -
Frontiers in Cardiovascular Medicine 2021Ischemic heart disease (IHD) is a considerable health burden worldwide with high mortality and morbidity. Treatments for IHD are mainly focused on decreasing oxygen...
Ischemic heart disease (IHD) is a considerable health burden worldwide with high mortality and morbidity. Treatments for IHD are mainly focused on decreasing oxygen demand or increasing myocardial oxygen supply, including pharmacological, interventional, and surgical treatment, but there are also some limitations. Therefore, it is important to find a simple, effective, and economical treatment. As non-invasive and safe physiotherapy, electrical stimulation (ES) has a promising application in the treatment of IHD. Current studies suggest that ES can affect the occurrence and development of IHD by promoting angiogenesis, regulating autophagy and apoptosis, inhibiting the inflammatory response and oxidative stress. In this review, we focus predominantly on the mechanism of ES and the current progress of ES therapy in IHD, furthermore, give a brief introduction to the forms of ES in clinical application.
PubMed: 34805318
DOI: 10.3389/fcvm.2021.761877 -
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 -
Ecotoxicology and Environmental Safety Oct 2023Adverse reactions to traditional Chinese medicine have hindered the healthy development and internationalization process of the traditional Chinese medicine industry....
Adverse reactions to traditional Chinese medicine have hindered the healthy development and internationalization process of the traditional Chinese medicine industry. The critical issue that needs to be solved urgently is to evaluate the safety of traditional Chinese medicine systematically and effectively. Podophyllotoxin (PPT) is a highly active compound extracted from plants of the genus Podophyllum such as Dysosma versipellis (DV). However, its high toxicity and toxicity to multiple target organs affect the clinical application, such as the liver and kidney. Based on the concurrent effects of PPT's medicinal activity and toxicity, it would be a good example to conduct a systematic review of its safety. Therefore, this study revolves around the Toxicological Evidence Chain (TEC) concept. Based on PPT as the main toxic constituent in DV, observe the objective toxicity impairment phenotype of animals. Evaluate the serum biochemical indicators and pathological tissue sections for substantial toxic damage results. Using metabolomics, lipidomics, and network toxicology to evaluate the nephrotoxicity of PPT from multiple perspectives systematically. The results showed that PPT-induced nephrotoxicity manifested as renal tubular damage, mainly affecting metabolic pathways such as glycerophospholipid metabolism and sphingolipid metabolism. PPT inhibits the autophagy process of kidney cells through the PI3K/Akt/mTOR and Nrf2/HO1 pathways and induces the activation of oxidative stress in the body, thereby causing nephrotoxic injury. This study fully verified the feasibility of the TEC concept for the safety and toxicity evaluation of traditional Chinese medicine. Provide a research template for systematically evaluating the safety of traditional Chinese medicine.
Topics: Animals; Rats; Kidney; NF-E2-Related Factor 2; Phosphatidylinositol 3-Kinases; Podophyllotoxin; Proto-Oncogene Proteins c-akt; TOR Serine-Threonine Kinases; Podophyllum; Drugs, Chinese Herbal
PubMed: 37651795
DOI: 10.1016/j.ecoenv.2023.115392