scholarly journals Curcumin as a therapeutic agent: the evidence fromin vitro, animal and human studies

2010 ◽  
Vol 103 (11) ◽  
pp. 1545-1557 ◽  
Author(s):  
Jenny Epstein ◽  
Ian R. Sanderson ◽  
Thomas T. MacDonald
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Human Subjects ◽  
Complex Molecule ◽  
Dietary Factors ◽  
Major Constituent ◽  
Western World ◽  
Yellow Colour ◽  
Biological Targets

Curcumin is the active ingredient of turmeric. It is widely used as a kitchen spice and food colorant throughout India, Asia and the Western world. Curcumin is a major constituent of curry powder, to which it imparts its characteristic yellow colour. For over 4000 years, curcumin has been used in traditional Asian and African medicine to treat a wide variety of ailments. There is a strong current public interest in naturally occurring plant-based remedies and dietary factors related to health and disease. Curcumin is non-toxic to human subjects at high doses. It is a complex molecule with multiple biological targets and different cellular effects. Recently, its molecular mechanisms of action have been extensively investigated. It has anti-inflammatory, antioxidant and anti-cancer properties. Under some circumstances its effects can be contradictory, with uncertain implications for human treatment. While more studies are warranted to further understand these contradictions, curcumin holds promise as a disease-modifying and chemopreventive agent. We review the evidence for the therapeutic potential of curcumin fromin vitrostudies, animal models and human clinical trials.

scholarly journals Lasia spinosa Chemical Composition and Therapeutic Potential: A Literature-Based Review

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Rajib Hossain ◽  
Cristina Quispe ◽  
Jesús Herrera-Bravo ◽  
Md. Shahazul Islam ◽  
Chandan Sarkar ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Human Subjects ◽  
Uterine Cancer ◽  
Safety Data ◽  
Volatile Oil ◽  
Stomach Pain

Lasia spinosa (L.) is used ethnobotanically for the treatment of various diseases, including rheumatoid arthritis, inflammation of the lungs, bleeding cough, hemorrhoids, intestinal diseases, stomach pain, and uterine cancer. This review is aimed at summarizing phytochemistry and pharmacological data with their molecular mechanisms of action. A search was performed in databases such as PubMed, Science Direct, and Google Scholar using the keywords: “Lasia spinosa,” then combined with “ethnopharmacological use,” “phytochemistry,” and “pharmacological activity.” This updated review included studies with in vitro, ex vivo, and in vivo experiments with compounds of known concentration and highlighted pharmacological mechanisms. The research results showed that L. spinosa contains many important nutritional and phytochemical components such as alkanes, aldehydes, alkaloids, carotenoids, flavonoids, fatty acids, ketones, lignans, phenolics, terpenoids, steroids, and volatile oil with excellent bioactivity. The importance of this review lies in the fact that scientific pharmacological evidence supports the fact that the plant has antioxidant, anti-inflammatory, antimicrobial, cytotoxic, antidiarrheal, antihelminthic, antidiabetic, antihyperlipidemic, and antinociceptive effects, while protecting the gastrointestinal system and reproductive. Regarding future toxicological and safety data, more research is needed, including studies on human subjects. In light of these data, L. spinosa can be considered a medicinal plant with effective bioactives for the adjuvant treatment of various diseases in humans.

scholarly journals Alantolactone: A Natural Plant Extract as a Potential Therapeutic Agent for Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuan Cai ◽  
Kewa Gao ◽  
Bi Peng ◽  
Zhijie Xu ◽  
Jinwu Peng ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cancer Colorectal ◽  
Therapeutic Potential ◽  
Inhibitory Effects ◽  
Cytotoxic Effects ◽  
Cancer Breast ◽  
Anticancer Effects ◽  
Inula Helenium

Alantolactone (ALT) is a natural compound extracted from Chinese traditional medicine Inula helenium L. with therapeutic potential in the treatment of various diseases. Recently, in vitro and in vivo studies have indicated cytotoxic effects of ALT on various cancers, including liver cancer, colorectal cancer, breast cancer, etc. The inhibitory effects of ALT depend on several cancer-associated signaling pathways and abnormal regulatory factors in cancer cells. Moreover, emerging studies have reported several promising strategies to enhance the oral bioavailability of ALT, such as combining ALT with other herbs and using ALT-entrapped nanostructured carriers. In this review, studies on the anti-tumor roles of ALT are mainly summarized, and the underlying molecular mechanisms of ALT exerting anticancer effects on cells investigated in animal-based studies are also discussed.

scholarly journals Pharmacological Inhibition of Caspase-8 Suppresses Inflammation-Induced Angiogenesis in the Cornea

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 210
Author(s):  
Yunzhe Tian ◽  
He Li ◽  
Xiuxing Liu ◽  
Lihui Xie ◽  
Zhaohao Huang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Corneal Neovascularization ◽  
Caspase 8 ◽  
Inhibitory Effects ◽  
Toll Like Receptor 4 ◽  
Pharmacological Inhibition ◽  
Cytokines And Chemokines ◽  
Tnf Α

Inflammation-induced angiogenesis is closely related to many diseases and has been regarded as a therapeutic target. Caspase-8 has attracted increasing attention for its immune properties and therapeutic potential in inflammatory disorders. The aim of our study is to investigate the clinical application of pharmacological inhibition of caspase-8 and the underlying molecular mechanisms in inflammation-induced angiogenesis in the cornea. A model of alkali burn (AB)-induced corneal neovascularization (CNV) in C57BL/6 wild-type (WT) mice and toll-like receptor 4 knockout (Tlr4-/-) mice was used. We found that AB increased caspase-8 activity and the pharmacological inhibition of caspase-8 exerted substantial inhibitory effects on CNV, with consistent decreases in caspase-8 activity, inflammatory cell infiltration, macrophage recruitment and activation, VEGF-A, TNF-α, IL-1β, MIP-1, and MCP-1 expression in the cornea. In vitro, caspase-8 mediated TLR4–dependent chemokines and VEGF-A production by macrophages. The TLR4 knockout significantly alleviated CNV, suppressed caspase-8 activity and downregulated expression of inflammatory cytokines and chemokines after AB. Taken together, these findings provide the first demonstration that the pharmacological inhibition of caspase-8 suppresses inflammation-induced angiogenesis and support the use of a pharmacological caspase-8 inhibitor as a novel clinical treatment for CNV and other angiogenic disorders.

scholarly journals Determining the Effect of Pterostilbene on Insulin Secretion Using Chemoproteomics

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2885
Author(s):  
Chiara Cassiano ◽  
Daniela Eletto ◽  
Alessandra Tosco ◽  
Raffaele Riccio ◽  
Maria Chiara Monti ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Beta Cells ◽  
Metabolic Disorders ◽  
Therapeutic Potential ◽  
Pharmacological Profile ◽  
Biological Targets ◽  
Cell Assays ◽  
Potential Applications ◽  
Insulin Dependent

Pterostilbene, the 3,5-dimethoxy derivative of resveratrol, is a well-known polyphenolic compound, mainly found in blueberries, grapevines, and Pterocarpus marsupium heartwood, which has recently attracted a great deal of attention due to its wide bio-pharmacological profile. Moreover, pterostilbene is more lipophilic than resveratrol, with a consequently better bioavailability and a more interesting therapeutic potential. In this work, a chemoproteomic approach, based on affinity chromatography, was applied on pterostilbene in the attempt to identify the biological targets responsible for its bioactivity. On this basis, syntaxins, a group of proteins involved in the formation of SNARE complexes mediating vesicles exocytosis, were selected among the most interesting pterostilbene interactors. In vitro and in cell assays gave evidence of the pterostilbene ability to reduce insulin secretion on glucose-stimulated pancreatic beta cells, opening the way to potential applications of pterostilbene as a supplement in the care of insulin-dependent metabolic disorders.

scholarly journals miR-125b Suppresses Proliferation and Invasion by Targeting MCL1 in Gastric Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Shihua Wu ◽  
Feng Liu ◽  
Liming Xie ◽  
Yaling Peng ◽  
Xiaoyuan Lv ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Clinical Stage ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Progression

Understanding the molecular mechanisms underlying gastric cancer progression contributes to the development of novel targeted therapies. In this study, we found that the expression levels of miR-125b were strongly downregulated in gastric cancer and associated with clinical stage and the presence of lymph node metastases. Additionally, miR-125b could independently predict OS and DFS in gastric cancer. We further found that upregulation of miR-125b inhibited the proliferation and metastasis of gastric cancer cells in vitro and in vivo. miR-125b elicits these responses by directly targeting MCL1 (myeloid cell leukemia 1), which results in a marked reduction in MCL1 expression. Transfection of miR-125b sensitizes gastric cancer cells to 5-FU-induced apoptosis. By understanding the function and molecular mechanisms of miR-125b in gastric cancer, we may learn that miR-125b has the therapeutic potential to suppress gastric cancer progression and increase drug sensitivity to gastric cancer.

scholarly journals The Molecular Pathogenesis of Haemangioma

2021 ◽  
Author(s):  
◽  
Anasuya Vishvanath
Keyword(s):  
Growth Factor ◽  
Tyrosine Kinases ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Primary Tumour ◽  
Treatment Options ◽  
Janus Kinase ◽  
Stem Cell Population ◽  
Induced Apoptosis

<p>Haemangioma is a primary tumour of the microvasculature characterised by active angiogenesis and endothelial cell (EC)  proliferation followed by slow regression or involution whereby the newly formed blood vessels are gradually replaced by fibrofatty tissue. These developmental changes have been arbitrarily divided into the proliferative, involuting and involuted phases. The cellular and molecular events that initiate and regulate the proliferation and spontaneous involution of haemangioma remain poorly understood. This study examined the expression of a number of genes known to be associated with angiogenesis. These include members of the signal transducers and activators of transcription (STAT) protein family of transcription factors, STAT-3 and STAT-1, and the endothelial receptor tyrosine kinases, VEGFR-1 and VEGFR-2. While STAT-3, STAT-1 and VEGFR-1 expression was detected in all phases of haemangioma, VEGFR-2 expression was found to be abundant only during the proliferative phase and decreased with ongoing involution. In this study the cellular structures that form capillary-like outgrowths in an in vitro haemangioma explant model were characterised as haemangioma-derived mesenchymal stem cells (HaemDMSCs) while the cells obtained directly from dissociated proliferative haemangioma tissue were defined as haemangioma-derived endothelial progenitor cells (HaemDEPCs). This investigation showed that although the vascular endothelial growth factor (VEGF), a key growth factor for ECs, was able to maintain HaemDEPCs morphology and immunophenotype for a limited period, these cells eventually differentiated into HaemDMSCs, which subsequently differentiated into adipocytes. Furthermore, while VEGF induced significant capillary-like sprouting from tissue explants, both capillary-like sprouting and HaemDMSCs proliferation was inhibited by the addition of AG490, a Janus kinase (JAK) inhibitor which has also been shown to inhibit the STAT protein pathway. These findings indicate that the development and differentiation of a progenitor cell and a stem cell population underlies the aethiopathogenesis of haemangioma and that VEGF and STAT signalling is involved in the programmed life-cycle of haemangioma. The in vitro explant model for haemangioma offers an opportunity to study and identify novel treatment options for haemangioma. Interferon-alpha (IFN ) has been used to treat steroid-resistant haemangioma but is associated with serious side-affects. The tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been shown to specifically induce apoptosis of cancer cells while sparing normal cells. As IFN has previously been shown to sensitise cells to TRAIL-induced apoptosis, this study examined the efficacy of low dose IFN in combination with TRAIL in the in vitro explant model and also in the purified HaemDMSCs. Results showed that combining IFN with TRAIL led to synergistic inhibition of capillary-like outgrowth. These results indicate that IFN in combination with TRAIL serves as a potential treatment option for haemangioma. In contrast, HaemDMSCs were protected from TRAIL-induced killing. These cells were found to express high levels of the decoy receptors, osteoprotegerin (OPG) and decoy receptor 2 (DcR2). Increased OPG expression was also detected in the extracellular matrix and in the conditioned medium of HaemDMSCs. From these findings, we postulate that the increased level of extracellular OPG by HaemDMSCs is a stress response induced by their in vitro expansion and that secreted OPG functions as a protective shield preventing TRAIL action. The empirical and unsatisfactory nature of the current therapies for haemangioma underscores the importance of a scientific approach to this common tumour. A better understanding of the molecular mechanisms that govern haemangioma is of both clinical and biological interest as it may provide vital information with therapeutic potential for haemangioma and also for other angiogenesis-dependent conditions.</p>

scholarly journals Aryl hydrocarbon receptor signaling pathway plays important roles in the proliferative and metabolic properties of bone marrow mesenchymal stromal cells

2021 ◽  
Author(s):  
Yan Jia ◽  
Youshan Zhao ◽  
Zheng Zhang ◽  
Lei Shi ◽  
Ying Fang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Aryl Hydrocarbon Receptor ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Aryl Hydrocarbon ◽  
Receptor Signaling Pathway ◽  
Metabolic Properties

Abstract Bone marrow mesenchymal stromal cells (BMMSCs) are widely sourced and easily amplified in vitro; thus, they have a great potential in the treatment of hemopathies. Recent findings suggested that BMMSCs express the aryl hydrocarbon receptor (AHR). However, few studies have reported on the regulation of proliferative behaviors and metabolism by AHR in BMMSCs. In the present study, we found that activating AHR reduced the proliferation of BMMSCs and enhanced their mitochondrial function, whereas inhibiting AHR exerted the opposite effects. This study may provide the basis for further unveiling the molecular mechanisms and therapeutic potential of AHR in BMMSCs.

The Importance and Bioavailability of Phytoferritin-Bound Iron in Cereals and Legume Foods

2007 ◽  
Vol 77 (3) ◽  
pp. 152-157 ◽  
Author(s):  
Lönnerdal
Keyword(s):  
Iron Absorption ◽  
Proteolytic Enzymes ◽  
Human Subjects ◽  
Human Study ◽  
Heme Iron ◽  
Dietary Factors ◽  
Whole Body ◽  
Significant Difference ◽  
Staple Foods

Ferritin is present in several types of plants in low concentrations, but it is possible to enhance this content by plant breeding, or by inserting the gene for ferritin into staple foods. Since each ferritin molecule can bind thousands of iron atoms, this may be a sustainable means to increase the iron content of plants. Before launching such efforts it is important to determine whether ferritin-bound iron is bioavailable. We assessed this in vitro using Caco-2 cells and in vivo using radiolabeled ferritin and whole body counting in human subjects. In Caco-2 cells, we found that dietary factors affecting iron absorption, such as ascorbic acid, phytate, and calcium, had very limited effect on iron uptake from intact ferritin, suggesting that ferritin-bound iron is absorbed via a mechanism different from that of non-heme iron. Using in vitro digestion, we found that ferritin was relatively resistant against proteolytic enzymes. Binding of ferritin to Caco-2 cells was found to be saturable and the kinetics for binding characteristic for a receptor-mediated process. In human subjects, we found that iron absorption from animal ferritin was similar to that from ferrous sulfate, suggesting that iron is well absorbed from ferritin. We did not find any significant difference between iron absorption from ferritin reconstituted with high-phosphate (plant-type) and low-phosphate (animal-type) ferritin mineral, suggesting that plant ferritin-iron is bioavailable. In a subsequent human study we also found that iron from purified soybean ferritin given in a meal was as well absorbed as ferrous iron. In conclusion, iron is well absorbed from phytoferritin and may represent a means of biofortification of staple foods.

Cordycepin in Anticancer Research: Molecular Mechanism of Therapeutic Effects

2020 ◽  
Vol 27 (6) ◽  
pp. 983-996 ◽  
Author(s):  
Md. Asaduzzaman Khan ◽  
Mousumi Tania
Keyword(s):  
Anticancer Activity ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Cancer Drug ◽  
Therapeutic Effects ◽  
Anticancer Activities ◽  
Cancer Cell Growth ◽  
Ongoing Research

Background: Cordycepin is a nucleotide analogue from Cordyceps mushrooms, which occupies a notable place in traditional medicine. Objective: In this review article, we have discussed the recent findings on the molecular aspects of cordycepin interactions with its recognized cellular targets, and possible mechanisms of its anticancer activity. Methods: We have explored databases like pubmed, google scholar, scopus and web of science for the update information on cordycepin and mechanisms of its anticancer activity, and reviewed in this study. Results: Cordycepin has been widely recognized for its therapeutic potential against many types of cancers by various mechanisms. More specifically, cordycepin can induce apoptosis, resist cell cycle and cause DNA damage in cancer cells, and thus kill or control cancer cell growth. Also cordycepin can induce autophagy and modulate immune system. Furthermore, cordycepin also inhibits tumor metastasis. Although many success stories of cordycepin in anticancer research in vitro and in animal model, and there is no successful clinical trial yet. Conclusion: Ongoing research studies have reported highly potential anticancer activities of cordycepin with numerous molecular mechanisms. The in vitro and in vivo success of cordycepin in anticancer research might influence the clinical trials of cordycepin, and this molecule might be used for development of future cancer drug.

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