scholarly journals Molecular Mechanisms and Therapeutic Effects of (−)-Epicatechin and Other Polyphenols in Cancer, Inflammation, Diabetes, and Neurodegeneration

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Joseph Shay ◽  
Hosam A. Elbaz ◽  
Icksoo Lee ◽  
Steven P. Zielske ◽  
Moh H. Malek ◽  
...  
Keyword(s):  
Natural Products ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Epigallocatechin Gallate ◽  
Therapeutic Effects ◽  
Oxygen Species ◽  
The World ◽  
Map Kinase Pathway ◽  
Kinase Pathway ◽  
Insight Into

With recent insight into the mechanisms involved in diseases, such as cardiovascular disease, cancer, stroke, neurodegenerative diseases, and diabetes, more efficient modes of treatment are now being assessed. Traditional medicine including the use of natural products is widely practiced around the world, assuming that certain natural products contain the healing properties that may in fact have a preventative role in many of the diseases plaguing the human population. This paper reviews the biological effects of a group of natural compounds called polyphenols, including apigenin, epigallocatechin gallate, genistein, and (−)-epicatechin, with a focus on the latter. (−)-Epicatechin has several unique features responsible for a variety of its effects. One of these is its ability to interact with and neutralize reactive oxygen species (ROS) in the cell. (−)-Epicatechin also modulates cell signaling including the MAP kinase pathway, which is involved in cell proliferation. Mutations in this pathway are often associated with malignancies, and the use of (−)-epicatechin holds promise as a preventative agent and as an adjunct for chemotherapy and radiation therapy to improve outcome. This paper discusses the potential of some phenolic compounds to maintain, protect, and possibly reinstate health.

scholarly journals A Mep2-dependent Transcriptional Profile Links Permease Function to Gene Expression during Pseudohyphal Growth in Saccharomyces cerevisiae

2008 ◽  
Vol 19 (7) ◽  
pp. 3028-3039 ◽  
Author(s):  
Julian C. Rutherford ◽  
Gordon Chua ◽  
Timothy Hughes ◽  
Maria E. Cardenas ◽  
Joseph Heitman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Map Kinase ◽  
Molecular Mechanisms ◽  
Nutrient Sensing ◽  
Transcriptional Profile ◽  
Regulatory Function ◽  
Pseudohyphal Growth ◽  
Epistasis Analysis ◽  
Map Kinase Pathway ◽  
Kinase Pathway

The ammonium permease Mep2 is required for the induction of pseudohyphal growth, a process in Saccharomyces cerevisiae that occurs in response to nutrient limitation. Mep2 has both a transport and a regulatory function, supporting models in which Mep2 acts as a sensor of ammonium availability. Potentially similar ammonium permease-dependent regulatory cascades operate in other fungi, and they may also function in animals via the homologous Rh proteins; however, little is known about the molecular mechanisms that mediate ammonium sensing. We show that Mep2 is localized to the cell surface during pseudohyphal growth, and it is required for both filamentous and invasive growth. Analysis of site-directed Mep2 mutants in residues lining the ammonia-conducting channel reveal separation of function alleles (transport and signaling defective; transport-proficient/signaling defective), indicating transport is necessary but not sufficient to sense ammonia. Furthermore, Mep2 overexpression enhances differentiation under normally repressive conditions and induces a transcriptional profile that is consistent with activation of the mitogen-activated protein (MAP) kinase pathway. This finding is supported by epistasis analysis establishing that the known role of the MAP kinase pathway in pseudohyphal growth is linked to Mep2 function. Together, these data strengthen the model that Mep2-like proteins are nutrient sensing transceptors that govern cellular differentiation.

(−)-Epigallocatechin gallate inhibits prostaglandin D2-stimulated HSP27 induction via suppression of the p44/p42 MAP kinase pathway in osteoblasts

2007 ◽  
Vol 77 (3-4) ◽  
pp. 173-179 ◽  
Author(s):  
Junichi Yamauchi ◽  
Shinji Takai ◽  
Rie Matsushima-Nishiwaki ◽  
Yoshiteru Hanai ◽  
Tomoaki Doi ◽  
...  
Keyword(s):  
Map Kinase ◽  
Epigallocatechin Gallate ◽  
Prostaglandin D2 ◽  
Map Kinase Pathway ◽  
Kinase Pathway

scholarly journals Profiled tea extracts exemplifying the importance of characterizing food bioactives: opinion piece

2019 ◽  
Vol 5 ◽  
pp. 1-5 ◽  
Author(s):  
Shiming Li ◽  
Alexander Gosslau ◽  
Klaus Lange ◽  
Chi-Tang Ho
Keyword(s):  
Natural Products ◽  
Single Molecule ◽  
Functional Foods ◽  
Biological Effects ◽  
Biological Evaluation ◽  
Therapeutic Agents ◽  
Therapeutic Effects ◽  
Chemical Identification ◽  
Component Identification

Natural products from food and herbs have been used as functional food and medicine for centuries, much earlier than any of the current single molecule drugs in the market. Historically, natural products are the dominant resources of current global pharmaceutical market. Examples include world’s most commonly used drugs such as aspirin, penicillin and taxol. In viewing the increasing attraction and exponentially growing need for functional foods and effective medicines, the potential for natural products to serve as safe and effective preventive and therapeutic agents is of much interest. However, the importance in the phytochemical characterization of plant origin and associated extracts containing multiple phytochemicals in research and product development in this field has been plagued by overwhelmingly focusing on their biological effects. More than often inconsistent and invalid biological results are provided without chemical component identification and validation. Hence it is vital to characterize and identify the ingredients in the plant extracts – food bioactives- that play critical roles in promoting health or having therapeutic effects. The combination of chemical identification and biological evaluation is the key to having valid and consistent results in elucidating health beneficial properties of a plant or its extracts and also a key to have a meaningful comparison among similar studies due to the use of the same standard. Herein, we use tea as examples demonstrating the importance of phytochemical profiling and associated bioactive property of functional foods.

scholarly journals Targeting Autophagy with Natural Compounds in Cancer: A Renewed Perspective from Molecular Mechanisms to Targeted Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiang Xie ◽  
Yi Chen ◽  
Huidan Tan ◽  
Bo Liu ◽  
Ling-Li Zheng ◽  
...  
Keyword(s):  
Natural Products ◽  
Cancer Therapy ◽  
Signaling Pathways ◽  
Small Molecule ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Natural Compounds ◽  
Therapeutic Effects ◽  
Therapeutic Benefits ◽  
Small Molecule Drugs

Natural products are well-characterized to have pharmacological or biological activities that can be of therapeutic benefits for cancer therapy, which also provide an important source of inspiration for discovery of potential novel small-molecule drugs. In the past three decades, accumulating evidence has revealed that natural products can modulate a series of key autophagic signaling pathways and display therapeutic effects in different types of human cancers. In this review, we focus on summarizing some representative natural active compounds, mainly including curcumin, resveratrol, paclitaxel, Bufalin, and Ursolic acid that may ultimately trigger cancer cell death through the regulation of some key autophagic signaling pathways, such as RAS-RAF-MEK-ERK, PI3K-AKT-mTOR, AMPK, ULK1, Beclin-1, Atg5 and p53. Taken together, these inspiring findings would shed light on exploiting more natural compounds as candidate small-molecule drugs, by targeting the crucial pathways of autophagy for the future cancer therapy.

scholarly journals Marine Natural Products: A Source of Novel Anticancer Drugs

Marine Drugs ◽  
2019 ◽  
Vol 17 (9) ◽  
pp. 491 ◽  
Author(s):  
Shaden A. M. Khalifa ◽  
Nizar Elias ◽  
Mohamed A. Farag ◽  
Lei Chen ◽  
Aamer Saeed ◽  
...  
Keyword(s):  
Natural Products ◽  
Anticancer Drugs ◽  
Marine Natural Products ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Marine Organisms ◽  
New Drugs ◽  
Bioactive Metabolites ◽  
Chemical Structures ◽  
The Impact

Cancer remains one of the most lethal diseases worldwide. There is an urgent need for new drugs with novel modes of action and thus considerable research has been conducted for new anticancer drugs from natural sources, especially plants, microbes and marine organisms. Marine populations represent reservoirs of novel bioactive metabolites with diverse groups of chemical structures. This review highlights the impact of marine organisms, with particular emphasis on marine plants, algae, bacteria, actinomycetes, fungi, sponges and soft corals. Anti-cancer effects of marine natural products in in vitro and in vivo studies were first introduced; their activity in the prevention of tumor formation and the related compound-induced apoptosis and cytotoxicities were tackled. The possible molecular mechanisms behind the biological effects are also presented. The review highlights the diversity of marine organisms, novel chemical structures, and chemical property space. Finally, therapeutic strategies and the present use of marine-derived components, its future direction and limitations are discussed.

An Appraisal of Current Pharmacological Perspectives of Sesamol: A Review

2020 ◽  
Vol 20 (11) ◽  
pp. 988-1000 ◽  
Author(s):  
Bellamkonda Bosebabu ◽  
Sri Pragnya Cheruku ◽  
Mallikarjuna Rao Chamallamudi ◽  
Madhavan Nampoothiri ◽  
Rekha R. Shenoy ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Biological Effects ◽  
Hepatoprotective Activity ◽  
In Vivo Studies ◽  
Therapeutic Effects ◽  
Pharmacological Effects ◽  
Bioactive Constituents ◽  
Anti Inflammatory

Sesame (Sesamum indicum L.) seeds have been authenticated for its medicinal value in both Chinese and Indian systems of medicine. Its numerous potential nutritional benefits are attributed to its main bioactive constituents, sesamol. As a result of those studies, several molecular mechanisms are emerging describing the pleiotropic biological effects of sesamol. This review summarized the most interesting in vitro and in vivo studies on the biological effects of sesamol. The present work summarises data available from Pubmed and Scopus database. Several molecular mechanisms have been elucidated describing the pleiotropic biological effects of sesamol. Its major therapeutic effects have been elicited in managing oxidative and inflammatory conditions, metabolic syndrome and mood disorders. Further, compelling evidence reflected the ability of sesamol in inhibiting proliferation of the inflammatory cell, prevention of invasion and angiogenesis via affecting multiple molecular targets and downstream mechanisms. Sesamol is a safe, non‐toxic chemical that mediates anti‐inflammatory effects by down‐regulating the transcription of inflammatory markers such as cytokines, redox status, protein kinases, and enzymes that promote inflammation. In addition, sesamol also induces apoptosis in cancer cells via mitochondrial and receptor‐mediated pathways, as well as activation of caspase cascades. In the present review, several pharmacological effects of sesamol are summarised namely, antioxidant, anti-cancer, neuroprotective, cardioprotective, anti-inflammatory, hypolipidemic, radioprotective, anti-aging, anti-ulcer, anti-dementia, anti-depressant, antiplatelet, anticonvulsant, anti-anxiolytic, wound healing, cosmetic (skin whitening), anti-microbial, matrix metalloproteinase (MMPs) inhibition, hepatoprotective activity and other biological effects. Here we have summarized the proposed mechanism behind these pharmacological effects.

scholarly journals Functions for Cdc42p BEM adaptors in regulating a differentiation-type MAP kinase pathway

2020 ◽  
Vol 31 (6) ◽  
pp. 491-510 ◽  
Author(s):  
Sukanya Basu ◽  
Beatriz González ◽  
Boyang Li ◽  
Garrett Kimble ◽  
Keith G. Kozminski ◽  
...  
Keyword(s):  
Map Kinase ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Mapk Pathway ◽  
Map Kinase Pathway ◽  
Effector Pathways ◽  
Kinase Pathway ◽  
Insight Into

How Rho GTPases are directed to effector pathways is an important question. We show here that BEM-type adaptors play unique roles in sequentially directing Cdc42 to an effector MAPK pathway. Our study may provide insight into Rho GTPase specification in other systems.

scholarly journals New Insight into the Molecular Mechanisms of the Biological Effects of DNA Minor Groove Binders

PLoS ONE ◽  
2011 ◽  
Vol 6 (10) ◽  
pp. e25822 ◽  
Author(s):  
Xinbo Zhang ◽  
Siyu Crystal Zhang ◽  
Dejun Sun ◽  
Jiang Hu ◽  
Anil Wali ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Biological Effects ◽  
Minor Groove ◽  
Dna Minor Groove ◽  
Minor Groove Binders ◽  
Groove Binders ◽  
Insight Into

Pim Kinases Mediate Viability Signals Downstream of the Tyrosine Kinase Oncogenes BCR-ABL and FLT3-ITD.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 557-557
Author(s):  
Martin Sattler ◽  
Emily Babendreier ◽  
Stephanie C. Chu ◽  
Jessica L. Gramlich ◽  
Klaus Podar ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Growth ◽  
Cell Lines ◽  
Tyrosine Kinases ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Hematopoietic Cells ◽  
Target Cells ◽  
Therapeutic Effects ◽  
Pim Kinases

Abstract Pim1 and Pim2 belong to a family of serine/threonine kinases that are overexpressed in many leukemias. Pim1 has previously been shown to cooperate with the v-myc oncogene to transform hematopoietic cells with murine transforming viruses and overexpression of Pim2 has been shown to induce growth factor independence in a factor dependent murine BaF3 cell line. Protein expression of both Pim1 and Pim2 is low or absent in non-transformed hematopoietic cells but was found to be rapidly increased upon transformation by BCR-ABL or FLT3 with an internal tandem duplication (ITD). The exact contribution of the Pim kinases to transformation in these cells is unknown. BaF3 cell lines were created that stably expressed either BCR-ABL or FLT3-ITD tyrosine kinases, and in which either Pim1 or Pim2 could be induced with doxycycline. Treatment of BCR-ABL or FLT3-ITD expressing cells with small molecule kinase inhibitors specific for either ABL or FLT3 led to inhibition of cell growth, increased apoptosis, and downregulation of Pim expression as expected. However, if Pim2, and to a lesser extent, Pim1 expression was maintained by doxycycline, there was a substantial increase in both viability and cell growth. The molecular mechanisms by which Pim proteins exhibit their effects on target cells are not known. Using parental growth factor dependent BaF3 cell lines with doxycycline inducible Pim1 and Pim2, we show that expression of either of the Pim proteins is sufficient, by itself, to reduce apoptosis and induce modest cell growth. The effects of Pim overexpression on several pathways known to be associated with viability were studied. We found that while Pim over-expression does not activate Akt, it does result in the phosphorylation of a known Akt target, GSK-3β, a regulator of cell cycle progression by targeting the stability of cyclin D proteins. This suggests that Pim proteins may mediate their biological effects through regulation of components in the phosphatidylinositol-3′ kinase signaling cascade, independent of Akt activation. These results further suggest that upregulation of Pim kinases significantly contributes to transformation. Inhibition of Pim kinases could have beneficial therapeutic effects in leukemias.

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