scholarly journals Inhibition of Pro-Inflammatory Cytokines by Metabolites of Streptomycetes—A Potential Alternative to Current Anti-Inflammatory Drugs?

2020 ◽  
Vol 8 (5) ◽  
pp. 621
Author(s):  
Jiří Hrdý ◽  
Lenka Súkeníková ◽  
Petra Petrásková ◽  
Olga Novotná ◽  
David Kahoun ◽  
...  
Keyword(s):  
Human Monocyte ◽  
Current Treatment ◽  
Attractive Alternative ◽  
Anti Cancer ◽  
Dependent Inhibition ◽  
Apoptotic Effect ◽  
Potential Alternative ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Drug Leads

Current treatment of chronic diseases includes, among others, application of cytokines, monoclonal antibodies, cellular therapies, and immunostimulants. As all the underlying mechanisms of a particular diseases are not always fully clarified, treatment can be inefficient and associated with various, sometimes serious, side effects. Small secondary metabolites produced by various microbes represent an attractive alternative as future anti-inflammatory drug leads. Compared to current drugs, they are cheaper, can often be administered orally, but still can keep a high target-specificity. Some compounds produced by actinomycetes or fungi have already been used as immunomodulators—tacrolimus, sirolimus, and cyclosporine. This work documents strong anti-inflammatory features of another secondary metabolite of streptomycetes—manumycin-type polyketides. We compared the effect of four related compounds: manumycin A, manumycin B, asukamycin, and colabomycin E on activation and survival of human monocyte/macrophage cell line THP-1. The anti-cancer effect of manucycine A has been demonstrated; the immunomodulatory capacities of manumycin A are obvious when using micromolar concentrations. The application of all four compounds in 0.25–5 μM concentrations leads to efficient, concentration-dependent inhibition of IL-1β and TNF expression in THP-1 upon LPS stimulation, while the three latter compounds show a significantly lower pro-apoptotic effect than manumycin A. We have demonstrated the anti-inflammatory capacity of selected manumycin-type polyketides.

scholarly journals The Synergistic Anti-Apoptosis Effects of Amniotic Epithelial Stem Cell Conditioned Medium and Ponesimod on the Oligodendrocyte Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Fahimeh Safaeinejad ◽  
Sareh Asadi ◽  
Shiva Ghafghazi ◽  
Hassan Niknejad
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Combination Therapy ◽  
Conditioned Medium ◽  
Annexin V ◽  
Current Treatment ◽  
Epithelial Stem Cells ◽  
Apoptotic Effect ◽  
S1p Receptor ◽  
Anti Inflammatory

Multiple sclerosis is a chronic inflammatory and neurodegenerative disease of the central nervous system. The current treatment of Multiple sclerosis is based on anti-inflammatory disease-modifying treatments, which can not regenerate myelin and eventually neurons. So, we need new approaches for axonal protection and remyelination. Amniotic epithelial stem cells amniotic epithelial cells, as a neuroprotective and neurogenic agent, are a proper source in tissue engineering and regenerative medicine. Due to differentiation capability and secretion of growth factors, AECs can be a candidate for the treatment of MS. Moreover, sphingosine-1-phosphate (S1P) receptor modulators were recently approved by FDA for MS. Ponesimod is an S1P receptor-1 modulator that acts selectively as an anti-inflammatory agent and provides a suitable microenvironment for the function of the other neuroprotective agents. In this study, due to the characteristics of AECs, they are considered a treatment option in MS. The conditioned medium of AECs concurrently with ponesimod was used to evaluate the viability of the oligodendrocyte cell line after induction of cell death by cuprizone. Cell viability after treatment by conditioned medium and ponesimod was increased compared to untreated groups. Also, the results showed that combination therapy with CM and ponesimod had a synergistic anti-apoptotic effect on oligodendrocyte cells. The combination treatment with CM and ponesimod reduced the expression of caspase-3, caspase-8, Bax, and Annexin V proteins and increased the relative BCL-2/Bax ratio, indicating inhibition of apoptosis as a possible mechanism of action. Based on these promising results, combination therapy with amniotic stem cells and ponesimode could be a proper alternative for multiple sclerosis treatment.

Inflammatory Biomarkers in Atrial Fibrillation

2019 ◽  
Vol 26 (5) ◽  
pp. 837-854 ◽  
Author(s):  
Effimia Zacharia ◽  
Nikolaos Papageorgiou ◽  
Adam Ioannou ◽  
Gerasimos Siasos ◽  
Spyridon Papaioannou ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Plasma Levels ◽  
Large Scale ◽  
Inflammatory Biomarkers ◽  
Inflammatory Pathways ◽  
Inflammatory State ◽  
Anti Inflammatory ◽  
Underlying Mechanisms

During the last few years, a significant number of studies have attempted to clarify the underlying mechanisms that lead to the presentation of atrial fibrillation (AF). Inflammation is a key component of the pathophysiological processes that lead to the development of AF; the amplification of inflammatory pathways triggers AF, and, in tandem, AF increases the inflammatory state. Indeed, the plasma levels of several inflammatory biomarkers are elevated in patients with AF. In addition, the levels of specific inflammatory biomarkers may provide information regarding to the AF duration. Several small studies have assessed the role of anti-inflammatory treatment in atrial fibrillation but the results have been contradictory. Large-scale studies are needed to evaluate the role of inflammation in AF and whether anti-inflammatory medications should be routinely administered to patients with AF.

Role of Resveratrol in Modulating microRNAs in Human Diseases: From Cancer to Inflammatory Disorder

2020 ◽  
Vol 28 (2) ◽  
pp. 360-376 ◽  
Author(s):  
Atefeh Amiri ◽  
Maryam Mahjoubin-Tehran ◽  
Zatollah Asemi ◽  
Alimohammad Shafiee ◽  
Sarah Hajighadimi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Antioxidant Activities ◽  
Natural Compounds ◽  
Therapeutic Effects ◽  
Inflammatory Disorder ◽  
Inflammatory Disorders ◽  
Therapeutic Modalities ◽  
Anti Cancer ◽  
Current Therapies ◽  
Anti Inflammatory

: Cancer and inflammatory disorders are two important public health issues worldwide with significant socio.economic impacts. Despite several efforts, the current therapeutic platforms are associated with severe limitations. Therefore, developing new therapeutic strategies for the treatment of these diseases is a top priority. Besides current therapies, the utilization of natural compounds has emerged as a new horizon for the treatment of cancer and inflammatory disorders as well. Such natural compounds could be used either alone or in combination with the standard cancer therapeutic modalities such as chemotherapy, radiotherapy, and immunotherapy. Resveratrol is a polyphenolic compound that is found in grapes as well as other foods. It has been found that this medicinal agent displays a wide pharmacological spectrum, including anti-cancer, anti-inflammatory, anti-microbial, and antioxidant activities. Recently, clinical and pre-clinical studies have highlighted the anti-cancer and anti-inflammatory effects of resveratrol. Increasing evidence revealed that resveratrol exerts its therapeutic effects by targeting various cellular and molecular mechanisms. Among cellular and molecular targets that are modulated by resveratrol, microRNAs (miRNAs) have appeared as key targets. MiRNAs are short non-coding RNAs that act as epigenetic regulators. These molecules are involved in many processes that are involved in the initiation and progression of cancer and inflammatory disorders. Herein, we summarized various miRNAs that are directly/indirectly influenced by resveratrol in cancer and inflammatory disorders.

Natural Sesquiterpene Lactones in the Prevention and Treatment of Inflammatory Disorders and cancer: A Systematic Study of this Emerging Therapeutic Approach based on Chemical and Pharmacological Aspect

2020 ◽  
Vol 17 (9) ◽  
pp. 1102-1116
Author(s):  
Sudip Kumar Mandal ◽  
Utsab Debnath ◽  
Amresh Kumar ◽  
Sabu Thomas ◽  
Subhash Chandra Mandal ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Biological Activities ◽  
Sesquiterpene Lactones ◽  
Structural Diversity ◽  
Cancer Drug ◽  
Cancer Drug Discovery ◽  
Anti Cancer ◽  
Drug Discovery Program ◽  
Anti Inflammatory ◽  
Family Based

Background and Introduction: Sesquiterpene lactones are a class of secondary metabolite that contains sesquiterpenoids and lactone ring as pharmacophore moiety. A large group of bioactive secondary metabolites such as phytopharmaceuticals belong to this category. From the Asteraceae family-based medicinal plants, more than 5,000 sesquiterpene lactones have been reported so far. Sesquiterpene lactone-based pharmacophore moieties hold promise for broad-spectrum biological activities against cancer, inflammation, parasitic, bacterial, fungal, viral infection and other functional disorders. Moreover, these moiety based phytocompounds have been highlighted with a new dimension in the natural drug discovery program worldwide after the 2015 Medicine Nobel Prize achieved by the Artemisinin researchers. Objective: These bitter substances often contain an α, β-unsaturated-γ-lactone as a major structural backbone, which in recent studies has been explored to be associated with anti-tumor, cytotoxic, and anti-inflammatory action. Recently, the use of sesquiterpene lactones as phytomedicine has been increased. This study will review the prospect of sesquiterpene lactones against inflammation and cancer. Methods: Hence, we emphasized on the different features of this moiety by incorporating its structural diversity on biological activities to explore structure-activity relationships (SAR) against inflammation and cancer. Results: How the dual mode of action such as anti-inflammatory and anti-cancer has been exhibitedby these phytopharmaceuticals will be forecasted in this study. Furthermore, the correlation of anti-inflammatory and anti-cancer activity executed by the sesquiterpene lactones for fruitful phytotherapy will also be revealed in the present review in the milieu of pharmacophore activity relation and pharmacodynamics study as well. Conclusion: So, these metabolites are paramount in phytopharmacological aspects. The present discussion on the future prospect of this moiety based on the reported literature could be a guide for anti-inflammatory and anti-cancer drug discovery programs for the upcoming researchers.

Novel Findings of Anti-cancer Property of Propofol

2018 ◽  
Vol 18 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Jiaqiang Wang ◽  
Chien-shan Cheng ◽  
Yan Lu ◽  
Xiaowei Ding ◽  
Minmin Zhu ◽  
...  
Keyword(s):  
General Anesthesia ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Intravenous Anesthetic ◽  
The Past ◽  
Anti Cancer ◽  
Underlying Mechanisms ◽  
Recent Attention

Background: Propofol, a widely used intravenous anesthetic agent, is traditionally applied for sedation and general anesthesia. Explanation: Recent attention has been drawn to explore the effect and mechanisms of propofol against cancer progression in vitro and in vivo. Specifically, the proliferation-inhibiting and apoptosis-inducing properties of propofol in cancer have been studied. However, the underlying mechanisms remain unclear. Conclusion: This review focused on the findings within the past ten years and aimed to provide a general overview of propofol's malignance-modulating properties and the potential molecular mechanisms.

scholarly journals Evaluation of Dimer of Epicatechin from an Endophytic Fungus Curvularia australiensis FC2AP on Acute Toxicity Levels, Anti-Inflammatory and Anti-Cervical Cancer Activity in Animal Models

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 654
Author(s):  
Vellingiri Manon Mani ◽  
Arockiam Jeyasundar Parimala Gnana Soundari ◽  
Balamuralikrishnan Balasubramanian ◽  
Sungkwon Park ◽  
Utthapon Issara ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Acute Toxicity ◽  
Endophytic Fungus ◽  
Lethal Dose ◽  
Chemotherapeutic Agents ◽  
Cancer Drug ◽  
Dependent Manner ◽  
Anti Cancer ◽  
Albino Mice ◽  
Anti Inflammatory

Cervical cancer, as the most frequent cancer in women globally and accounts almost 14% in India. It can be prevented or treated with vaccines, radiation, chemotherapy, and brachytherapy. The chemotherapeutic agents cause adverse post effects by the destruction of the neighboring normal cells or altering the properties of the cells. In order to reduce the severity of the side effects caused by the chemically synthesized therapeutic agents, the current research developed an anti-cancer agent dimer of epicatechin (DoE), a natural bioactive secondary metabolite (BSM) mediated from an endophytic fungus Curvularia australiensis FC2AP. The investigation has initiated with the evaluation of inhibiting the angiogenesis which is a main activity in metastasis, and it was assessed through Hen’s Egg Test on Chorio Allantoic Membrane (HET-CAM) test; the BSM inhibited the growth of blood vessels in the developing chick embryo. Further the DoE was evaluated for its acute toxicity levels in albino mice, whereas the survival dose was found to be 1250 mg/kg and the lethal dose was 1500 mg/kg body weight of albino mice; hematological, biochemical, and histopathological analyses were assessed. The anti-inflammatory responses of the DoE were evaluated in carrageenan induced Wistar rats and the reduction of inflammation occurred in a dose-dependent manner. By fixing the effective dose for anti-inflammation analysis, the DoE was taken for the anti-cervical cancer analysis in benzo (a) pyrene induced female Sprague-Dawley rats for 60 days trial. After the stipulated days, the rats were taken for hematological antioxidants, lipid peroxidation (LPO), member bound enzymes, cervical histopathological and carcinogenic markers analyses. The results specified that the DoE has the capability of reducing the tumor in an efficient way. This is the first report of flavonoid-DoE production from an endophytic fungus C. australiensis has the anticancer potentiality and it can be stated as anti-cancer drug.

scholarly journals Vitamin E beyond Its Antioxidant Label

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 634
Author(s):  
Anca Ungurianu ◽  
Anca Zanfirescu ◽  
Georgiana Nițulescu ◽  
Denisa Margină
Keyword(s):  
Vitamin E ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Protective Effects ◽  
Cellular Effects ◽  
Inflammatory Status ◽  
Anti Cancer ◽  
Key Factor ◽  
Exciting Potential ◽  
Underlying Mechanisms

Vitamin E, comprising tocopherols and tocotrienols, is mainly known as an antioxidant. The aim of this review is to summarize the molecular mechanisms and signaling pathways linked to inflammation and malignancy modulated by its vitamers. Preclinical reports highlighted a myriad of cellular effects like modulating the synthesis of pro-inflammatory molecules and oxidative stress response, inhibiting the NF-κB pathway, regulating cell cycle, and apoptosis. Furthermore, animal-based models have shown that these molecules affect the activity of various enzymes and signaling pathways, such as MAPK, PI3K/Akt/mTOR, JAK/STAT, and NF-κB, acting as the underlying mechanisms of their reported anti-inflammatory, neuroprotective, and anti-cancer effects. In clinical settings, not all of these were proven, with reports varying considerably. Nonetheless, vitamin E was shown to improve redox and inflammatory status in healthy, diabetic, and metabolic syndrome subjects. The anti-cancer effects were inconsistent, with both pro- and anti-malignant being reported. Regarding its neuroprotective properties, several studies have shown protective effects suggesting vitamin E as a potential prevention and therapeutic (as adjuvant) tool. However, source and dosage greatly influence the observed effects, with bioavailability seemingly a key factor in obtaining the preferred outcome. We conclude that this group of molecules presents exciting potential for the prevention and treatment of diseases with an inflammatory, redox, or malignant component.

scholarly journals Finding an easy way to harmonize: a review of advances in clinical research and combination strategies of EZH2 inhibitors

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Chen Li ◽  
Yan Wang ◽  
Yueqing Gong ◽  
Tengrui Zhang ◽  
Jiaqi Huang ◽  
...  
Keyword(s):  
Treatment Modalities ◽  
Preclinical Studies ◽  
Combination Therapies ◽  
Tumor Treatment ◽  
Antitumor Effects ◽  
Therapeutic Modalities ◽  
Combination Strategies ◽  
Anti Cancer ◽  
Underlying Mechanisms ◽  
The Individual

AbstractEnhancer of zeste homolog 2 inhibitors (EZH2i) have garnered increased attention owing to their anticancer activity by targeting EZH2, a well-known cancer-promoting factor. However, some lymphomas are resistant to EZH2i, and EZH2i treatment alone is ineffective in case of EZH2-overexpressing solid tumors. The anti-cancer efficacy of EZH2i may be improved through safe and effective combinations of these drugs with other treatment modalities. Preclinical evidence indicates that combining EZH2i with other therapies, such as immunotherapy, chemotherapy, targeted therapy, and endocrine therapy, has complementary or synergistic antitumor effects. Therefore, elucidating the underlying mechanisms of the individual constituents of the combination therapies is fundamental for their clinical application. In this review, we have summarized notable clinical trials and preclinical studies using EZH2i, their progress, and combinations of EZH2i with different therapeutic modalities, aiming to provide new insights for tumor treatment.

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