Punicalagin Regulates Signaling Pathways in Inflammation-Associated Chronic Diseases

Inflammation is a complex biological defense system associated with a series of chronic diseases such as cancer, arthritis, diabetes, cardiovascular and neurodegenerative diseases. The extracts of pomegranate fruit and peel have been reported to possess health-beneficial properties in inflammation-associated chronic diseases. Punicalagin is considered to be the major active component of pomegranate extracts. In this review we have focused on recent studies into the therapeutic effects of punicalagin on inflammation-associated chronic diseases and the regulatory roles in NF-κB, MAPK, IL-6/JAK/STAT3 and PI3K/Akt/mTOR signaling pathways. We have concluded that punicalagin may be a promising therapeutic compound in preventing and treating inflammation-associated chronic diseases, although further clinical studies are required.

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From Menopause to Neurodegeneration—Molecular Basis and Potential Therapy

International Journal of Molecular Sciences ◽

10.3390/ijms22168654 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8654

Author(s):

Yu-Jung Cheng ◽

Chieh-Hsin Lin ◽

Hsien-Yuan Lane

Keyword(s):

Neurodegenerative Diseases ◽

Hormone Therapy ◽

Signaling Pathways ◽

Steroid Hormones ◽

Molecular Mechanisms ◽

Steroid Hormone ◽

Steroid Hormone Receptors ◽

Signal Pathways ◽

Therapeutic Effects ◽

The Brain

The impacts of menopause on neurodegenerative diseases, especially the changes in steroid hormones, have been well described in cell models, animal models, and humans. However, the therapeutic effects of hormone replacement therapy on postmenopausal women with neurodegenerative diseases remain controversial. The steroid hormones, steroid hormone receptors, and downstream signal pathways in the brain change with aging and contribute to disease progression. Estrogen and progesterone are two steroid hormones which decline in circulation and the brain during menopause. Insulin-like growth factor 1 (IGF-1), which plays an import role in neuroprotection, is rapidly decreased in serum after menopause. Here, we summarize the actions of estrogen, progesterone, and IGF-1 and their signaling pathways in the brain. Since the incidence of Alzheimer’s disease (AD) is higher in women than in men, the associations of steroid hormone changes and AD are emphasized. The signaling pathways and cellular mechanisms for how steroid hormones and IGF-1 provide neuroprotection are also addressed. Finally, the molecular mechanisms of potential estrogen modulation on N-methyl-d-aspartic acid receptors (NMDARs) are also addressed. We provide the viewpoint of why hormone therapy has inconclusive results based on signaling pathways considering their complex response to aging and hormone treatments. Nonetheless, while diagnosable AD may not be treatable by hormone therapy, its preceding stage of mild cognitive impairment may very well be treatable by hormone therapy.

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The Protective Effects of Green Tea Catechins in the Management of Neurodegenerative Diseases: A Review

Current Drug Discovery Technologies ◽

10.2174/1570163815666180219115453 ◽

2019 ◽

Vol 16 (1) ◽

pp. 57-65 ◽

Cited By ~ 3

Author(s):

Tahereh Farkhondeh ◽

Hanieh Shaterzadeh Yazdi ◽

Saeed Samarghandian

Keyword(s):

Neurodegenerative Diseases ◽

Signaling Pathways ◽

Green Tea ◽

Molecular Mechanisms ◽

Main Role ◽

Related Factor ◽

Protective Effects ◽

Tea Catechins ◽

Green Tea Catechins ◽

And Control

Background: The therapeutic strategies to manage neurodegenerative diseases remain limited and it is necessary to discover new agents for their prevention and control. Oxidative stress and inflammation play a main role in the pathogenesis of neurodegenerative diseases. The aim of this study is to review the effects of green tea catechins against the Neurodegenerative Diseases. Methods: In this study, we extensively reviewed all articles on the terms of Green tea, catechins, CNS disorders, and different diseases in PubMed, Science Direct, Scopus, and Google Scholar databases between the years 1990 and 2017. Results: The present study found that catechins, the major flavonoids in green tea, are powerful antioxidants and radical scavengers which possess the potential roles in the management of neurodegenerative diseases. Catechins modulate the cellular and molecular mechanisms through the inflammation-related NF-&#954;B and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. Conclusion: The findings of the present review shows catechins could be effective against neurodegenerative diseases due to their antioxidation and anti-inflammation effects and the involved biochemical pathways including Nrf2 and NF-kB signaling pathways.<P>

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Phosphoinositides signaling modulates microglial actin remodeling and phagocytosis in Alzheimer’s disease

Cell Communication and Signaling ◽

10.1186/s12964-021-00715-0 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Smita Eknath Desale ◽

Subashchandrabose Chinnathambi

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurodegenerative Diseases ◽

Signaling Pathways ◽

Amyloid Β ◽

Dietary Fatty Acids ◽

Receptor Expression ◽

Actin Binding ◽

Actin Remodeling ◽

Protein Deposits

AbstractAlzheimer’s disease is one of the neurodegenerative diseases, characterized by the accumulation of abnormal protein deposits, which disrupts signal transduction in neurons and other glia cells. The pathological protein in neurodegenerative diseases, Tau and amyloid-β contribute to the disrupted microglial signaling pathways, actin cytoskeleton, and cellular receptor expression. The important secondary messenger lipids i.e., phosphatidylinositols are largely affected by protein deposits of amyloid-β in Alzheimer’s disease. Phosphatidylinositols are the product of different phosphatidylinositol kinases and the state of phosphorylation at D3, D4, and D5 positions of inositol ring. Phosphatidylinositol 3,4,5-triphosphate (PI 3, 4, 5-P3) involves in phagocytic cup formation, cell polarization, whereas Phosphatidylinositol 4,5-bisphosphate (PI 4, 5-P2)-mediates the process of phagosomes formation and further its fusion with early endosome.. The necessary activation of actin-binding proteins such as Rac, WAVE complex, and ARP2/3 complex for the actin polymerization in the process of phagocytosis, migration is regulated and maintained by PI 3, 4, 5-P3 and PI 4, 5-P2. The ratio and types of fatty acid intake can influence the intracellular secondary lipid messengers along with the cellular content of phaphatidylcholine and phosphatidylethanolamine. The Amyloid-β deposits and extracellular Tau seeds disrupt phosphatidylinositides level and actin cytoskeletal network that hamper microglial-signaling pathways in AD. We hypothesize that being a lipid species intracellular levels of phosphatidylinositol would be regulated by dietary fatty acids. Further we are interested to understand phosphoinositide-based signaling cascades in phagocytosis and actin remodeling.

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Enhanced Bioavailability and Efficacy of Silymarin Solid Dispersion in Rats with Acetaminophen-Induced Hepatotoxicity

Pharmaceutics ◽

10.3390/pharmaceutics13050628 ◽

2021 ◽

Vol 13 (5) ◽

pp. 628

Author(s):

Im-Sook Song ◽

So-Jeong Nam ◽

Ji-Hyeon Jeon ◽

Soo-Jin Park ◽

Min-Koo Choi

Keyword(s):

Alkaline Phosphatase ◽

Polyethylene Glycol ◽

Oral Administration ◽

Solid Dispersion ◽

Active Component ◽

Efflux Pump ◽

Therapeutic Effects ◽

Permeation Enhancer ◽

Efflux Ratio ◽

Polyethylene Glycol 1000

We evaluated the bioavailability, liver distribution, and efficacy of silymarin-D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) solid dispersion (silymarin-SD) in rats with acetaminophen-induced hepatotoxicity (APAP) compared with silymarin alone. The solubility of silybin, the major and active component of silymarin, in the silymarin-SD group increased 23-fold compared with the silymarin group. The absorptive permeability of silybin increased by 4.6-fold and its efflux ratio decreased from 5.5 to 0.6 in the presence of TPGS. The results suggested that TPGS functioned as a solubilizing agent and permeation enhancer by inhibiting efflux pump. Thus, silybin concentrations in plasma and liver were increased in the silymarin-SD group and liver distribution increased 3.4-fold after repeated oral administration of silymarin-SD (20 mg/kg as silybin) for five consecutive days compared with that of silymarin alone (20 mg/kg as silybin). Based on higher liver silybin concentrations in the silymarin-SD group, the therapeutic effects of silymarin-SD in hepatotoxic rats were evaluated and compared with silymarin administration only. Elevated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels were significantly decreased by silymarin-SD, silymarin, and TPGS treatments, but these decreases were much higher in silymarin-SD animals than in those treated with silymarin or TPGS. In conclusion, silymarin-SD (20 mg/kg as silybin, three times per day for 5 days) exhibited hepatoprotective properties toward hepatotoxic rats and these properties were superior to silymarin alone, which may be attributed to increased solubility, enhanced intestinal permeability, and increased liver distribution of the silymarin-SD formulation.

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Beneficial Role of Carica papaya Extracts and Phytochemicals on Oxidative Stress and Related Diseases: A Mini Review

Biology ◽

10.3390/biology10040287 ◽

2021 ◽

Vol 10 (4) ◽

pp. 287

Author(s):

Yew Rong Kong ◽

Yong Xin Jong ◽

Manisha Balakrishnan ◽

Zhui Ken Bok ◽

Janice Kwan Kah Weng ◽

...

Keyword(s):

Oxidative Stress ◽

Signaling Pathways ◽

Chronic Diseases ◽

Carica Papaya ◽

Antioxidant Properties ◽

Natural Antioxidants ◽

The Body ◽

Health Conditions ◽

Chemical Components ◽

Impaired Wound Healing

Oxidative stress is a result of disruption in the balance between antioxidants and pro-oxidants in which subsequently impacting on redox signaling, causing cell and tissue damages. It leads to a range of medical conditions including inflammation, skin aging, impaired wound healing, chronic diseases and cancers but these conditions can be managed properly with the aid of antioxidants. This review features various studies to provide an overview on how Carica papaya help counteract oxidative stress via various mechanisms of action closely related to its antioxidant properties and eventually improving the management of various oxidative stress-related health conditions. Carica papaya is a topical plant species discovered to contain high amounts of natural antioxidants that can usually be found in their leaves, fruits and seeds. It contains various chemical compounds demonstrate significant antioxidant properties including caffeic acid, myricetin, rutin, quercetin, α-tocopherol, papain, benzyl isothiocyanate (BiTC), and kaempferol. Therefore, it can counteract pro-oxidants via a number of signaling pathways that either promote the expression of antioxidant enzymes or reduce ROS production. These signaling pathways activate the antioxidant defense mechanisms that protect the body against both intrinsic and extrinsic oxidative stress. To conclude, Carica papaya can be incorporated into medications or supplements to help manage the health conditions driven by oxidative stress and further studies are needed to investigate the potential of its chemical components to manage various chronic diseases.

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Precision Medicine in Neurodegenerative Diseases: Some Promising Tips Coming from the microRNAs’ World

Cells ◽

10.3390/cells9010075 ◽

2019 ◽

Vol 9 (1) ◽

pp. 75 ◽

Cited By ~ 3

Author(s):

Nicoletta Nuzziello ◽

Loredana Ciaccia ◽

Maria Liguori

Keyword(s):

Neurodegenerative Diseases ◽

Precision Medicine ◽

Target Genes ◽

Drug Disposition ◽

Therapeutic Potential ◽

Response To Treatment ◽

Therapeutic Effects ◽

Exciting Potential ◽

The Central Nervous System ◽

Effective Use

Novel insights in the development of a precision medicine approach for treating the neurodegenerative diseases (NDDs) are provided by emerging advances in the field of pharmacoepigenomics. In this context, microRNAs (miRNAs) have been extensively studied because of their implication in several disorders related to the central nervous system, as well as for their potential role as biomarkers of diagnosis, prognosis, and response to treatment. Recent studies in the field of neurodegeneration reported evidence that drug response and efficacy can be modulated by miRNA-mediated mechanisms. In fact, miRNAs seem to regulate the expression of pharmacology target genes, while approved (conventional and non-conventional) therapies can restore altered miRNAs observed in NDDs. The knowledge of miRNA pharmacoepigenomics may offers new clues to develop more effective treatments by providing novel insights into interindividual variability in drug disposition and response. Recently, the therapeutic potential of miRNAs is gaining increasing attention, and miRNA-based drugs (for cancer) have been under observation in clinical trials. However, the effective use of miRNAs as therapeutic target still needs to be investigated. Here, we report a brief review of representative studies in which miRNAs related to therapeutic effects have been investigated in NDDs, providing exciting potential prospects of miRNAs in pharmacoepigenomics and translational medicine.

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11-epi-Sinulariolide Acetate Reduces Cell Migration and Invasion of Human Hepatocellular Carcinoma by Reducing the Activation of ERK1/2, p38MAPK and FAK/PI3K/AKT/mTOR Signaling Pathways

Marine Drugs ◽

10.3390/md12094783 ◽

2014 ◽

Vol 12 (9) ◽

pp. 4783-4798 ◽

Cited By ~ 22

Author(s):

Jen-Jie Lin ◽

Jui-Hsin Su ◽

Chi-Chu Tsai ◽

Yi-Jen Chen ◽

Ming-Hui Liao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Migration ◽

Signaling Pathways ◽

Mtor Signaling ◽

Human Hepatocellular Carcinoma ◽

Migration And Invasion ◽

Cell Migration And Invasion

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AKIP1 promotes cell proliferation, invasion, stemness and activates PI3K-Akt, MEK/ERK, mTOR signaling pathways in prostate cancer

10.21203/rs.3.rs-568302/v1 ◽

2021 ◽

Author(s):

Jiabin Zhao ◽

Binjiahui Zhao ◽

Limin Hou

Keyword(s):

Prostate Cancer ◽

Cell Proliferation ◽

Signaling Pathways ◽

Cancer Patients ◽

Rna Sequencing ◽

Mtor Signaling ◽

Sequencing Analysis ◽

Lncap Cells ◽

Oncogenic Signaling ◽

Interacting Protein

Abstract Background: The study aimed to examine the molecular mechanism and clinical significance of A-kinase interacting protein 1 (AKIP1) in prostate cancer. Methods: The effect of AKIP1 on cell proliferation, migration, invasion, apoptosis and stemness was determined by overexpressing and knocking down AKIP1 in LNCaP and 22Rv1 cells via lentivirus infection. Furthermore, differentially expressed genes (DEGs) by AKIP1 modification were determined using RNA sequencing. Besides, the correlation of AKIP1 with clinicopathological features and prognosis in 130 prostate cancer patients was assessed. Results: AKIP1 expression was increased in VCaP, LNCaP, DU145 cells while similar in 22Rv1 cells compared with RWPE-1 cells. Furthermore, AKIP1 overexpression promoted 22Rv1 and LNCaP cell proliferation, invasion, but inhibited apoptosis; meanwhile, AKIP1 overexpression increased CD133+ cell rate and enhanced spheres formation efficiency in 22Rv1 and LNCaP cells. Reversely, AKIP1 knockdown exhibited the opposite effect in 22Rv1 and LNCaP cells. Further RNA sequencing analysis exhibited that AKIP1-modified DEGs were enriched in the oncogenic signaling pathways related to prostate cancer, such as PI3K-Akt, MEK/ERK, mTOR signaling pathways. The following western blot indicated that AKIP1 overexpression activated while its knockdown blocked PI3K-Akt, MEK/ERK, mTOR signaling pathways in prostate cancer cells. Clinically, AKIP1 was upregulated in the prostate tumor tissues compared with paired adjacent tissues, and its tumor high expression correlated with increased pathological T, pathological N stage and poor prognosis in prostate cancer patients. Conclusion: AKIP1 promotes cell proliferation, invasion, stemness, activates PI3K-Akt, MEK/ERK, mTOR signaling pathways and correlates with worse tumor features and prognosis in prostate cancer.

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