Melatonin and inflammation—Story of a double‐edged blade

Journal of Pineal Research, Год журнала: 2018, Номер 65(4)

Опубликована: Сен. 22, 2018

Melatonin is an immune modulator that displays both pro- and anti-inflammatory properties. Proinflammatory actions, which are well documented by many studies in isolated cells or leukocyte-derived cell lines, can be assumed to enhance the resistance against pathogens. However, they detrimental autoimmune diseases. Anti-inflammatory actions of particular medicinal interest, because observed high-grade inflammation such as sepsis, ischemia/reperfusion, brain injury, also low-grade during aging neurodegenerative The mechanisms contributing effects manifold comprise various pathways secondary signaling. These include numerous antioxidant effects, downregulation inducible inhibition neuronal NO synthases, cyclooxygenase-2, high-mobility group box-1 signaling toll-like receptor-4 activation, prevention inflammasome NLRP3 NF-κB activation upregulation nuclear factor erythroid 2-related 2 (Nrf2). reflected proinflammatory cytokines. amyloid-β peptides reduced enhancing α-secretase β- γ-secretases. A role melatonin's seems associated with sirtuin-1 (SIRT1), shares known from melatonin additionally interferes mechanistic target rapamycin (mTOR) Notch, reduces expression lncRNA-CCL2. conclusion on a partial mediation SIRT1 supported repeatedly inhibitions sirtuin inhibitors knockdown.

Язык: Английский

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Curcumin as an anti‐inflammatory agent: Implications to radiotherapy and chemotherapy

Journal of Cellular Physiology, Год журнала: 2018, Номер 234(5), С. 5728 - 5740

Опубликована: Окт. 14, 2018

Abstract Cancer is the second cause of death worldwide. Chemotherapy and radiotherapy are most common modalities for treatment cancer. Experimental studies have shown that inflammation plays a central role in tumor resistance incidence several side effects following both chemotherapy radiotherapy. Inflammation resulting from responsible adverse events such as dermatitis, mucositis, pneumonitis, fibrosis, bone marrow toxicity. Chronic may also lead to development cancer during years after treatment. A number anti‐inflammatory drugs nonsteroidal agents been proposed alleviate chronic inflammatory reactions or chemotherapy. Curcumin well‐documented herbal agents. Studies curcumin can help management targets various mediators cyclooxygenase‐2, inducible nitric oxide synthase, nuclear factor κB (NF‐κB), thereby attenuating release proinflammatory profibrotic cytokines, suppressing production free radicals, which culminates amelioration tissue Through modulation NF‐κB its downstream signaling cascade, reduce angiogenesis, growth, metastasis. Low toxicity linked cytoprotective normal tissues. This protective action along with capacity this phytochemical sensitize cells makes it potential candidate use an adjuvant therapy. There evidence clinical trials suggesting utility acute dermatitis mucositis.

Язык: Английский

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Melatonin as an Anti-Inflammatory Agent Modulating Inflammasome Activation

International Journal of Endocrinology, Год журнала: 2017, Номер 2017, С. 1 - 13

Опубликована: Янв. 1, 2017

Inflammation may be defined as the innate response to harmful stimuli such pathogens, injury, and metabolic stress; its ultimate function is restore physiological homeostatic state. The exact aetiology leading development of inflammation not known, but a combination genetic, epigenetic, environmental factors seems play an important role in pathogenesis many inflammation-related clinical conditions. Recent studies suggest that different inflammatory diseases also involves inflammasomes, intracellular multiprotein complexes mediate activation caspases thereby inducing secretion proinflammatory cytokines. Melatonin, endogenous indoleamine, considered multitasking molecule with fundamental applications. It involved mood modulation, sexual behavior, vasomotor control, immunomodulation influences energy metabolism; moreover, it acts oncostatic antiaging molecule. Melatonin antioxidant widespread anti-inflammatory molecule, modulating both pro- cytokines pathophysiological This review, first, gives overview concerning growing importance melatonin inflammatory-mediated pathological conditions and, then, focuses on roles protective effects against inflammasomes particular, NLRP3 inflammasome.

Язык: Английский

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New insights in intestinal oxidative stress damage and the health intervention effects of nutrients: A review

Journal of Functional Foods, Год журнала: 2020, Номер 75, С. 104248 - 104248

Опубликована: Окт. 28, 2020

Oxidative stress occurs when there exists an imbalance between the generation and elimination of reactive oxygen species (ROS). As inevitable exposure to foreign substances microbial pathogens, intestine is a key resource ROS. Disproportionate long-term ROS lead various intestinal diseases, such as inflammatory bowel diseases (IBD), enteric infections, ischemic injury colorectal cancers. Natural nutrients including vitamins, proteins, fats, minerals phytochemicals provide numerous evidences that they can protect health alleviate damage caused by oxidative stress, which be developed novel functional foods. This review summarized recent research progress on insights causes, mechanisms intervention effects nutrients. has also given prospects new discovered with benefits might foods or possible nutraceutical agents.

Язык: Английский

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Oxidative stress, hormones, and effects of natural antioxidants on intestinal inflammation in inflammatory bowel disease

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Авг. 28, 2023

Inflammatory bowel disease (IBD) is a chronic, relapsing gastrointestinal (GI) disorder characterized by intestinal inflammation. The etiology of IBD multifactorial and results from complex interplay between mucosal immunity, environmental factors, host genetics. Future therapeutics for GI disorders, including IBD, that are driven oxidative stress require greater understanding the cellular molecular mechanisms mediated reactive oxygen species (ROS). In tract, stressors include infections pro-inflammatory responses, which boost ROS generation promoting production cytokines. Nuclear factor kappa B (NF-κB) nuclear erythroid 2–related 2 (Nrf2) represent two important signaling pathways in immune cells regulate numerous physiological processes, anti-inflammatory antioxidant activities. Natural compounds exhibit scavenging increase defense capacity to inhibit pro-oxidative enzymes, may be useful treatment. this review, we discuss various polyphenolic substances (such as resveratrol, curcumin, quercetin, green tea flavonoids, caffeic acid phenethyl ester, luteolin, xanthohumol, genistein, alpinetin, proanthocyanidins, anthocyanins, silymarin), phenolic thymol, alkaloids such berberine, storage polysaccharides tamarind xyloglucan, other phytochemicals represented isothiocyanate sulforaphane food/spices ginger, flaxseed oil), well hormones like melatonin target reduce inflammation occurring with IBD.

Язык: Английский

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Involvement of inflammasomes in tumor microenvironment and tumor therapies

Journal of Hematology & Oncology, Год журнала: 2023, Номер 16(1)

Опубликована: Март 17, 2023

Abstract Inflammasomes are macromolecular platforms formed in response to damage-associated molecular patterns (DAMPs) and pathogen-associated patterns, whose formation would cause maturation of interleukin-1 (IL-1) family members gasdermin D (GSDMD), leading IL-1 secretion pyroptosis respectively. Several kinds inflammasomes detecting different types dangers have been found. The activation is regulated at both transcription posttranscription levels, which crucial protecting the host from infections sterile insults. Present findings illustrated that involved not only infection but also pathology tumors implying an important link between inflammation tumor development. Generally, participate tumorigenesis, cell death, metastasis, immune evasion, chemotherapy, target therapy, radiotherapy. Inflammasome components upregulated some tumors, can be activated cancer cells other stromal by DAMPs, chemotherapy agents, radiation. In cases, inhibit progression initiating GSDMD-mediated stimulating signal-mediated anti-tumor immunity. However, signal recruits immunosuppressive subsets cases. We discuss conflicting results propose possible explanations. Additionally, we summarize interventions targeting inflammasome pathways preclinical clinical stages. Interventions promising for immunotherapy combination therapy.

Язык: Английский

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Significance of Melatonin in the Regulation of Circadian Rhythms and Disease Management

Molecular Neurobiology, Год журнала: 2024, Номер 61(8), С. 5541 - 5571

Опубликована: Янв. 11, 2024

Язык: Английский

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Combination of melatonin and rapamycin for head and neck cancer therapy: Suppression of AKT/mTOR pathway activation, and activation of mitophagy and apoptosis via mitochondrial function regulation

Journal of Pineal Research, Год журнала: 2017, Номер 64(3)

Опубликована: Дек. 16, 2017

Head and neck squamous cell carcinoma (HNSCC) clearly involves activation of the Akt mammalian target rapamycin (mTOR) signalling pathway. However, effectiveness treatment with mTOR inhibitor is often limited by chemoresistance. Melatonin suppresses neoplastic growth via different mechanisms in a variety tumours. In this study, we aimed to elucidate effects melatonin on rapamycin-induced HNSCC death identify potential cross-talk pathways. We analysed dose-dependent rapamycin-treated lines (Cal-27 SCC-9). These cells were treated 0.1, 0.5 or 1 mmol/L combined 20 nM rapamycin. further examined synergistic Cal-27 xenograft mice. Relationships between inhibition pathway, reactive oxygen species (ROS), apoptosis mitophagy reportedly increased cytotoxic HNSCC. Our results demonstrated that blocked negative feedback loop from specific downstream effector S6K1 signalling, which decreased viability, proliferation clonogenic capacity. Interestingly, melatonin-induced changes mitochondrial function, associated ROS production, increasing mitophagy. This led increase cellular differentiation. data indicated administration reduced rapamycin-associated toxicity healthy cells. Overall, our findings suggested could be used as an adjuvant agent rapamycin, improving while minimizing its side effects.

Язык: Английский

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Melatonin alleviates weanling stress in mice: Involvement of intestinal microbiota

Journal of Pineal Research, Год журнала: 2017, Номер 64(2)

Опубликована: Дек. 16, 2017

Abstract Melatonin influences intestinal microbiota and the pathogenesis of various diseases. This study was conducted to explore whether melatonin alleviates weanling stress through in a mouse model. supplementation mice (provided drinking water at dosage 0.2 mg/mL for 2 weeks) significantly improved body weight gain (1.4 ± 0.03 g/day group vs 1.2 0.06 control group) morphology (ie, villus length, crypt depth, ratio), but had little effect on proliferation or apoptosis cells, numbers Paneth cells goblet as well expression makers related enterocytes (sucrase) endocrine (chromogranin A peptide YY) ileum. serum levels amino acids stress‐related parameters (eg, SOD, TNF‐α, angiotensin I). 16S rRNA sequencing suggested that increased richness indices (observed species, Chao 1, ACE) shaped composition increase abundance Lactobacillus [19 3% 6 2% group]), which demonstrated using an ex vivo assay colonic loop assay. also influenced metabolism microbiota, such acid drug metabolism. More importantly, antibiotic‐treated germ‐free mice, failed affect morphology. reduced (by about 60%) bacterial load enterotoxigenic Escherichia coli (ETEC)‐infected ETEC antibiotic‐pretreated animals. In conclusion, affects gain, morphology, infection mice. The findings highlight importance mediating physiological functions host.

Язык: Английский

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The anti-inflammatory and antioxidant effects of melatonin on LPS-stimulated bovine mammary epithelial cells

PLoS ONE, Год журнала: 2017, Номер 12(5), С. e0178525 - e0178525

Опубликована: Май 25, 2017

Mastitis is the most prevalent disease in dairy cattle worldwide and not only causes huge economic losses industry but also threatens public health. To evaluate therapeutic potential of melatonin mastitis, we examined ability to protect bovine mammary epithelial cells (bMECs) from harmful effects lipopolysaccharide (LPS). We found that inhibited LPS-binding protein–CD14–TLR4 signaling pathway bMECs, which had opposing on pro-inflammatory anti-inflammatory mediators. Melatonin decreased LPS-induced expression cytokines, chemokines, positive acute-phase proteins (APPs), including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, granulocyte-monocyte colony-stimulating factor, chemokine CC motif ligand (CCL)2, CCL5, serum amyloid A, haptoglobin, C-reactive protein, ceruloplasmin, α-1 antitrypsin, increased cytokine IL-1Ra negative APP fibrinogen. In addition, dityrosine levels suppressed nitrite by upregulating Nrf2 heme oxygenase-1 antioxidant defense pathway. Finally, administration viability LPS-stimulated bMECs. These results suggest protects bMECs inflammatory oxidant stress damage provide evidence might have utility mastitis.

Язык: Английский

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