Novel molecular mechanisms for the adaptogenic effects of herbal extracts on isolated brain cells using systems biology

Phytomedicine, Journal Year: 2018, Volume and Issue: 50, P. 257 - 284

Published: Sept. 20, 2018

Adaptogens are natural compounds or plant extracts that increase adaptability and survival of organisms under stress. stimulate cellular organismal defense systems by activating intracellular extracellular signaling pathways expression stress-activated proteins neuropeptides. The effects adaptogens on mediators adaptive stress response longevity have been reported, but their stress-protective mechanisms still not fully understood.The aim this study was to identify key molecular adaptogenic plants traditionally used treat aging-related disorders, i.e., Rhodiola rosea, Eleutherococcus senticosus, Withania somnifera, Rhaponticum carthamoides, Bryonia alba.To investigate the underlying adaptogens, we conducted RNA sequencing profile gene alterations in T98G neuroglia cells upon treatment analyzed relevance deregulated genes stress-response using silico pathway analysis software.At least 88 3516 regulated were closely associated with (ASRSPs), including neuronal related corticotropin-releasing hormone, cAMP-mediated, protein kinase A, CREB; involving CXCR4, melatonin, nitric oxide synthase, GP6, Gαs, MAPK, neuroinflammation, neuropathic pain, opioids, renin-angiotensin, AMPK, calcium, synapses; dendritic cell maturation G-coupled receptor-mediated nutrient sensing enteroendocrine cells. All samples tested showed significant encoding neurohormones CRH, GNRH, UCN, G-protein-coupled other transmembrane receptors TLR9, PRLR, CHRNE, GP1BA, PLXNA4, a ligand-dependent nuclear receptor RORA, channels, transcription regulators FOS, FOXO6, SCX, STAT5A, ZFPM2, ZNF396, ZNF467, kinases MAPK10, MAPK13, MERTK, FLT1, PRKCH, ROS1, TTN), phosphatases PTPRD, PTPRR, peptidases, metabolic enzymes, chaperone (HSPA6), proteins, all which modulate numerous life processes, playing roles several canonical involved regulation homeostasis organisms. It is for first time report mechanism actions melatonin alike, activated acting through two membrane MT1 MT2 upregulation ligand-specific plays role intellectual disability, neurological retinopathy, hypertension, dyslipidemia, cancer, common aging. Furthermore, upregulated GNRH1, CHRM4, GPR19, VIPR2, TTN, commonly tested. We conclude an adaptation hormone important homeostasis. presumably worked as eustressors ("stress-vaccines") activate system inducing ASRSPs, then reciprocally protected from damage caused distress. Functional investigation interactive demonstrated ASRSPs stress-induced disorders such chronic inflammation, cardiovascular health, neurodegenerative cognitive impairment, cancer.This has elucidated genome-wide herbal brain culture. These data highlight consistent activation affected many modulation homeostasis, indicating ability modify prevent disorders. Overall, provides comprehensive look at exerts effects.

Language: Английский

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Current Perspective in the Discovery of Anti-aging Agents from Natural Products

Natural Products and Bioprospecting, Journal Year: 2017, Volume and Issue: 7(5), P. 335 - 404

Published: May 31, 2017

Aging is a process characterized by accumulating degenerative damages, resulting in the death of an organism ultimately. The main goal aging research to develop therapies that delay age-related diseases human. Since signaling pathways Caenorhabditis elegans (C. elegans), fruit flies and mice are evolutionarily conserved, compounds extending lifespan them intervening may be useful treating Natural products have special resource advantage with few side effect. Recently, many or extracts from natural slowing been reported. Here we summarized these their mechanisms increasing longevity C. other species, prospect developing anti-aging medicine products.

Language: Английский

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Polyphenols as Caloric Restriction Mimetics Regulating Mitochondrial Biogenesis and Mitophagy

Trends in Endocrinology and Metabolism, Journal Year: 2020, Volume and Issue: 31(7), P. 536 - 550

Published: March 17, 2020

Language: Английский

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Genetic Ablation of miR-33 Increases Food Intake, Enhances Adipose Tissue Expansion, and Promotes Obesity and Insulin Resistance

Cell Reports, Journal Year: 2018, Volume and Issue: 22(8), P. 2133 - 2145

Published: Feb. 1, 2018

While therapeutic modulation of miRNAs provides a promising approach for numerous diseases, the promiscuous nature raises concern over detrimental off-target effects. miR-33 has emerged as likely target treatment cardiovascular diseases. However, deleterious effects long-term anti-miR-33 therapies and predisposition miR-33−/− mice to obesity metabolic dysfunction exemplify possible pitfalls miRNA-based therapies. Our work an in-depth characterization explores mechanisms by which loss promotes insulin resistance in key tissues. Contrary previous reports, our data do not support direct role SREBP-1-mediated lipid synthesis promoting these Alternatively, adipose tissue mice, we observe increased pre-adipocyte proliferation, enhanced uptake, impaired lipolysis. Moreover, demonstrate that driving force behind abnormalities is food intake, can be prevented pair feeding with wild-type animals.

Language: Английский

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Autophagy, its mechanisms and regulation: Implications in neurodegenerative diseases

Ageing Research Reviews, Journal Year: 2017, Volume and Issue: 40, P. 64 - 74

Published: Sept. 19, 2017

Language: Английский

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