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Journal of Drug Targeting Sep 2023Renal fibrosis, characterised by glomerulosclerosis and tubulointerstitial fibrosis, is a typical pathological alteration in the progression of chronic kidney disease... (Review)
Review
Renal fibrosis, characterised by glomerulosclerosis and tubulointerstitial fibrosis, is a typical pathological alteration in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). However, the limited and expensive options for treating renal fibrosis place a heavy financial burden on patients and healthcare systems. Therefore, it is significant to find an effective treatment for renal fibrosis. Ferroptosis, a non-traditional form of cell death, has been found to play an important role in acute kidney injury (AKI), tumours, neurodegenerative diseases, and so on. Moreover, a growing body of research suggests that ferroptosis might be a potential target of renal fibrosis. Meanwhile, mitophagy is a type of selective autophagy that can selectively degrade damaged or dysfunctional mitochondria as a form of mitochondrial quality control, reducing the production of reactive oxygen species (ROS), the accumulation of which is the main cause of renal fibrosis. Additionally, as a receptor of mitophagy, NIX can release beclin1 to induce mitophagy, which can also bind to solute carrier family 7 member 11 (SLC7A11) to block the activity of cystine/glutamate antitransporter (system Xc-) and inhibit ferroptosis, thereby suggesting a link between mitophagy and ferroptosis. However, there have been only limited studies on the relationship among mitophagy, ferroptosis and renal fibrosis. In this paper, we review the mechanisms of mitophagy, and describe how ferroptosis and mitophagy are related to renal fibrosis in an effort to identify potential novel targets for the treatment of renal fibrosis.
Topics: Humans; Mitophagy; Ferroptosis; Acute Kidney Injury; Cystine; Mitochondria
PubMed: 37607069
DOI: 10.1080/1061186X.2023.2250574 -
Critical Reviews in Food Science and... 2019Considered as the "King of spices", black pepper ( L.) is a widely used spice which adds flavor of its own to dishes, and also enhances the taste of other ingredients....
Considered as the "King of spices", black pepper ( L.) is a widely used spice which adds flavor of its own to dishes, and also enhances the taste of other ingredients. has also been extensively explored for its biological properties and its bioactive phyto-compounds. There is, however, no updated compilation of these available data to provide a complete profile of the medicinal aspects of . This study endeavors to systematically review scientific data on the traditional uses, phytochemical composition, and pharmacological properties of Information was obtained using a combination of keywords recognized electronic databases (e.g., Science Direct and Google Scholar). Google search was also used. Books and online materials were also considered, and the literature search was restricted to the English language. The country with the highest number of traditional reports of for both human and veterinary medicine was India, mostly for menstrual and ear-nose-throat disorders in human and gastrointestinal disorders in livestock. The seeds and fruits were mostly used, and the preferred mode of preparation was in powdered form, pills or tablets, and paste. and its bioactive compounds were also found to possess important pharmacological properties. Antimicrobial activity was recorded against a wide range of pathogens via inhibition of biofilm, bacterial efflux pumps, bacterial swarming, and swimming motilities. Studies also reported its antioxidant effects against a series of reactive oxygen and nitrogen species including the scavenging of superoxide anion, hydrogen peroxide, nitric oxide, DPPH, ABTS, and reducing effect against ferric and molybdenum (VI). Improvement of antioxidant enzymes has also been reported. also exhibited anticancer effect against a number of cell lines from breast, colon, cervical, and prostate through different mechanisms including cytotoxicity, apoptosis, autophagy, and interference with signaling pathways. Its antidiabetic property has also been confirmed as well as hypolipidemic activity as evidenced by decrease in the level of cholesterol, triglycerides, and low-density lipoprotein and increase in high-density lipoprotein. also has anti-inflammatory, analgesic, anticonvulsant, and neuroprotective effects. The major bioactive compound identified in is piperine although other compounds are also present including piperic acid, piperlonguminine, pellitorine, piperolein B, piperamide, piperettine, and (-)-kusunokinin, which also showed biological potency. Most pharmacological studies were conducted ( = 60) while only 21 and 1 clinical trial were performed. Hence, more experiments using a pharmacokinetic and pharmacokinetic approach would be beneficial. As a conclusive remark, should not only be regarded as "King of spices" but can also be considered as part of the kingdom of medicinal agents, comprising a panoply of bioactive compounds with potential nutraceutical and pharmaceutical applications.
Topics: Animals; Databases, Factual; Dietary Supplements; Fruit; Humans; India; Medicine, East Asian Traditional; Phytochemicals; Piper nigrum; Plant Extracts
PubMed: 30740986
DOI: 10.1080/10408398.2019.1565489 -
International Journal of Molecular... Jun 2017Eukaryotes use autophagy as a mechanism for maintaining cellular homeostasis by degrading and recycling organelles and proteins. This process assists in the... (Review)
Review
Eukaryotes use autophagy as a mechanism for maintaining cellular homeostasis by degrading and recycling organelles and proteins. This process assists in the proliferation and survival of advanced cancers. There is mounting preclinical evidence that targeting autophagy can enhance the efficacy of many cancer therapies. Hydroxychloroquine (HCQ) is the only clinically-approved autophagy inhibitor, and this systematic review focuses on HCQ use in cancer clinical trials. Preclinical trials have shown that HCQ alone and in combination therapy leads to enhancement of tumor shrinkage. This has provided the base for multiple ongoing clinical trials involving HCQ alone and in combination with other treatments. However, due to its potency, there is still a need for more potent and specific autophagy inhibitors. There are multiple autophagy inhibitors in the pre-clinical stage at various stages of development. Additional studies on the mechanism of HCQ and other autophagy inhibitors are still required to answer questions surrounding how these agents will eventually be used in the clinic.
Topics: Animals; Antimalarials; Antineoplastic Agents; Autophagy; Clinical Trials as Topic; Humans; Hydroxychloroquine; Neoplasms
PubMed: 28621712
DOI: 10.3390/ijms18061279 -
Cancer Chemotherapy and Pharmacology Feb 2017Hydroxychloroquine (HCQ), the analog of chloroquine, augments the effect of chemotherapies and radiotherapy on various tumors identified in the current clinical trials.... (Review)
Review
PURPOSE
Hydroxychloroquine (HCQ), the analog of chloroquine, augments the effect of chemotherapies and radiotherapy on various tumors identified in the current clinical trials. Meanwhile, the toxicity of HCQ retinopathy raises concern worldwide. Thus, the potent autophagy inhibitors are urgently needed.
METHODS
A systematic review was related to 'hydroxychloroquine' or 'chloroquine' with 'clinical trials,' 'retinopathy' and 'new autophagy inhibitors.' This led to many cross-references involving HCQ, and these data have been incorporated into the following study.
RESULTS
Many preclinical studies indicate that the combination of HCQ with chemotherapies or radiotherapies may enhance the effect of anticancer, providing base for launching cancer clinical trials involving HCQ. The new and more sensitive diagnostic techniques report a prevalence of HCQ retinopathy up to 7.5%. Lys05, SAR405, verteporfin, VATG-027, mefloquine and spautin-1 may be potent autophagy inhibitors.
CONCLUSION
Additional mechanistic studies of HCQ in preclinical models are still required in order to answer these questions whether HCQ actually inhibits autophagy in non-selective tumors and whether the extent of inhibition would be sufficient to alter chemotherapy or radiotherapy sensitivity.
Topics: Autophagy; Clinical Trials as Topic; Humans; Hydroxychloroquine; Neoplasms; Retina
PubMed: 27889812
DOI: 10.1007/s00280-016-3197-1 -
International Journal of Molecular... Jan 2024The social burden of dementia is remarkable since it affects some 57.4 million people all over the world. Impairment of autophagy in age-related diseases, such as... (Review)
Review
The social burden of dementia is remarkable since it affects some 57.4 million people all over the world. Impairment of autophagy in age-related diseases, such as dementia, deserves deep investigation for the detection of novel disease-modifying approaches. Several drugs belonging to different classes were suggested to be effective in managing Alzheimer's disease (AD) by means of autophagy induction. Useful autophagy inducers in AD should be endowed with a direct, measurable effect on autophagy, have a safe tolerability profile, and have the capability to cross the blood-brain barrier, at least with poor penetration. According to the PRISMA 2020 recommendations, we propose here a systematic review to appraise the measurable effectiveness of autophagy inducers in the improvement of cognitive decline and neuropsychiatric symptoms in clinical trials and retrospective studies. The systematic search retrieved 3067 records, 10 of which met the eligibility criteria. The outcomes most influenced by the treatment were cognition and executive functioning, pointing at a role for metformin, resveratrol, masitinib and TPI-287, with an overall tolerable safety profile. Differences in sample power, intervention, patients enrolled, assessment, and measure of outcomes prevents generalization of results. Moreover, the domain of behavioral symptoms was found to be less investigated, thus prompting new prospective studies with homogeneous design. PROSPERO registration: CRD42023393456.
Topics: Humans; Alzheimer Disease; Cognition; Cognitive Dysfunction; Prospective Studies; Retrospective Studies; Autophagy; Neurodegenerative Diseases
PubMed: 38279266
DOI: 10.3390/ijms25021264 -
Frontiers in Physiology 2022Autophagy is a highly conserved process that is indispensable for cell survival, embryonic development, and tissue homeostasis. Activation of autophagy protects cells...
Autophagy is a highly conserved process that is indispensable for cell survival, embryonic development, and tissue homeostasis. Activation of autophagy protects cells against oxidative stress and is a major adaptive response to injury. When autophagy is dysregulated by factors such as smoking, environmental insults and aging, it can lead to enhanced formation of aggressors and production of reactive oxygen species (ROS), resulting in oxidative stress and oxidative damage to cells. ROS activates autophagy, which in turn promotes cell adaptation and reduces oxidative damage by degrading and circulating damaged macromolecules and dysfunctional cell organelles. The cellular response triggered by oxidative stress includes changes in signaling pathways that ultimately regulate autophagy. Chronic obstructive pulmonary disease (COPD) is the most common lung disease among the elderly worldwide, with a high mortality rate. As an induced response to oxidative stress, autophagy plays an important role in the pathogenesis of COPD. This review discusses the regulation of oxidative stress and autophagy in COPD, and aims to provide new avenues for future research on target-specific treatments for COPD.
PubMed: 36225291
DOI: 10.3389/fphys.2022.1004275 -
BioMed Research International 2021Probiotics are living microorganisms increasingly used to treat or modulate different diseases or disorders because of their benefits and also low adverse reaction, and...
Probiotics are living microorganisms increasingly used to treat or modulate different diseases or disorders because of their benefits and also low adverse reaction, and their positive and protective effects on various cells and tissues have been reported. The mechanisms by which probiotics exert their beneficial effects in different cells and tissues were investigated, and autophagy is one of the main mechanisms to induce their positive effects. Autophagy is a conserved process that occurs in all eukaryotic cells and plays an essential role in homeostasis and cell survival by degrading damaged and dysfunctional intracellular organelles. On the other hand, the role of autophagy is diverse in different tissues and situations, and cell death derived from autophagy has been observed in some cells. This search was done in PubMed, WOS, and Scopus using the keywords probiotic, microbiota, and autophagy. The search strategy was focused on the in vitro and animal model studies, and the included filters were English language publications and full-text articles (by June 2020). Studies that investigated other underlying mechanisms except autophagy were excluded. Among more than 105 papers, 24 studies were considered eligible for more evaluation. The obtained results indicated that most studies were performed on intestinal cell lines or tissue compared with other types of cell lines and tissue. This review article discusses our current understanding of the probiotic effects through autophagy in different cell lines and tissues that would be a useful guide to daily and clinical usage of these living microorganisms, but despite promising results of this systematic review, further studies need to assess this issue. This systematic review has demonstrated that autophagy is an effective mechanism in inducing beneficial effects of probiotics in different tissues.
Topics: Animals; Autophagy; Homeostasis; Humans; Microbiota; Probiotics
PubMed: 34901266
DOI: 10.1155/2021/2931580 -
Frontiers in Genetics 2022Heparan sulfate modified proteins or proteoglycans (HSPGs) are an abundant class of cell surface and extracellular matrix molecules. They serve important co-receptor...
Heparan sulfate modified proteins or proteoglycans (HSPGs) are an abundant class of cell surface and extracellular matrix molecules. They serve important co-receptor functions in the regulation of signaling as well as membrane trafficking. Many of these activities directly affect processes associated with neurodegeneration including uptake and export of Tau protein, disposition of Amyloid Precursor Protein-derived peptides, and regulation of autophagy. In this review we focus on the impact of HSPGs on autophagy, membrane trafficking, mitochondrial quality control and biogenesis, and lipid metabolism. Disruption of these processes are a hallmark of Alzheimer's disease (AD) and there is evidence that altering heparan sulfate structure and function could counter AD-associated pathological processes. Compromising presenilin function in several systems has provided instructive models for understanding the molecular and cellular underpinnings of AD. Disrupting presenilin function produces a constellation of cellular deficits including accumulation of lipid, disruption of autophagosome to lysosome traffic and reduction in mitochondrial size and number. Inhibition of heparan sulfate biosynthesis has opposing effects on all these cellular phenotypes, increasing mitochondrial size, stimulating autophagy flux to lysosomes, and reducing the level of intracellular lipid. These findings suggest a potential mechanism for countering pathology found in AD and related disorders by altering heparan sulfate structure and influencing cellular processes disrupted broadly in neurodegenerative disease. Vertebrate and invertebrate model systems, where the cellular machinery of autophagy and lipid metabolism are conserved, continue to provide important translational guideposts for designing interventions that address the root cause of neurodegenerative pathology.
PubMed: 36699460
DOI: 10.3389/fgene.2022.1012706 -
Journal of Applied Toxicology : JAT Apr 2023In this review, we summarized the current literature on the impact of phenothiazine derivatives on autophagy in vitro. Phenothiazines are antipsychotic drugs used in the... (Review)
Review
In this review, we summarized the current literature on the impact of phenothiazine derivatives on autophagy in vitro. Phenothiazines are antipsychotic drugs used in the treatment of schizophrenia, which is related to altered neurotransmission and dysregulation of neuronal autophagy. Thus, phenothiazine derivatives can impact autophagy. We identified 35 papers, where the use of the phenothiazines in the in vitro autophagy assays on normal and cancer cell lines, Caenorhabditis elegans, and zebrafish were discussed. Chlorpromazine, fluphenazine, mepazine, methotrimeprazine, perphenazine, prochlorperazine, promethazine, thioridazine, trifluoperazine, and novel derivatives can modulate autophagy. Stimulation of autophagy by phenothiazines may be either mammalian target of rapamycin (mTOR)-dependent or mTOR-independent. The final effect depends on the used concentration as well as the cell line. A further investigation of the mechanisms of autophagy regulation by phenothiazine derivatives is required to understand the biological actions and to increase the therapeutic potential of this class of drugs.
Topics: Animals; Antipsychotic Agents; Zebrafish; Promazine; Phenothiazines; Chlorpromazine; Mammals
PubMed: 36165981
DOI: 10.1002/jat.4397 -
Phytomedicine : International Journal... Dec 2022Eugenol (1-allyl-4-hydroxy-3-methoxybenzene) is an important simple phenolic compound mainly derived from Syzygium aromaticum and many other plants. It is traditionally... (Review)
Review
BACKGROUND
Eugenol (1-allyl-4-hydroxy-3-methoxybenzene) is an important simple phenolic compound mainly derived from Syzygium aromaticum and many other plants. It is traditionally used in ayurveda and aromatherapy for the healing of many health problems. It also has significant applications in dentistry, agriculture, and flavour industry. This simple phenol has an eclectic range of pharmacological properties, such as antioxidant, anti-inflammatory, and anticancer activities. It is regarded as safe by the Food and Agricultural Organization of the United Nations due to its non-carcinogenic and non-mutagenic properties.
PURPOSE
The aim of this comprehensive review is to present a critical and systematic assessment of the antitumor ability of eugenol and its associated molecular targets in various cancers.
METHODS
It was carried out following the preferred reporting items for systematic reviews and meta-analysis guidelines. Risk of bias assessment was performed using the SYstematic review centre for laboratory animal experimentation guidelines. The literature search was performed in standard databases such as Science Direct, PubMed, Google Scholar, Scopus, and Web of Science using the keywords 'eugenol' or 'eugenol essential oil' and 'anti-cancer properties of eugenol'.
RESULTS
The scientific information from fifty-three studies was encompassed in the present review work. Eugenol exhibits significant anticancer effects in a variety of biological pathways, namely apoptosis, autophagy, cell cycle progression, inflammation, invasion, and metastasis. Eugenol-induced apoptosis has been noticed in osteosarcoma, skin tumors, melanoma, leukemia, gastric and mast cells. It decreases the expression of cyclin D1, cyclin B, proliferating cell nuclear antigen, nuclear factor-ƙB, inhibitor of nuclear factor ƙB, and B-cell lymphoma-2. Eugenol increases the expression of B-cell lymphoma-2 (BCL-2) associated X, BH3-interacting domain death agonist, BCL-2 associated agonist of cell death, apoptotic protease activating factor 1, cytochrome c, p21, and p53.
CONCLUSION
The anticancer potential exhibited by eugenol is mainly attributed to its anti-metastatic, anti-proliferative, anti-angiogenic, anti-inflammatory, cell cycle arrest, apoptotic, and autophagic effects. Hence, the use of eugenol alone or along with other chemotherapeutic anticancer agents is found to be very effective in cancer therapy.
Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Apoptotic Protease-Activating Factor 1; Cyclin B; Cyclin D1; Cytochromes c; Eugenol; Neoplasms; Oils, Volatile; Phenols; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-bcl-2; Tumor Suppressor Protein p53
PubMed: 36152592
DOI: 10.1016/j.phymed.2022.154456