Molecular Mechanisms of Possible Action of Phenolic Compounds in COVID-19 Protection and Prevention

The worldwide outbreak of COVID-19 was caused by a pathogenic virus called Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Therapies against SARS-CoV-2 target the virus or human cells or the immune system. However, therapies based on specific antibodies, such as vaccines and monoclonal antibodies, may become inefficient enough when the virus changes its antigenicity due to mutations. Polyphenols are the major class of bioactive compounds in nature, exerting diverse health effects based on their direct antioxidant activity and their effects in the modulation of intracellular signaling. There are currently numerous clinical trials investigating the effects of polyphenols in prophylaxis and the treatment of COVID-19, from symptomatic, via moderate and severe COVID-19 treatment, to anti-fibrotic treatment in discharged COVID-19 patients. Antiviral activities of polyphenols and their impact on immune system modulation could serve as a solid basis for developing polyphenol-based natural approaches for preventing and treating COVID-19.

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Immune System Stimulation by Oncolytic Rodent Protoparvoviruses

Viruses ◽

10.3390/v11050415 ◽

2019 ◽

Vol 11 (5) ◽

pp. 415 ◽

Cited By ~ 4

Author(s):

Assia Angelova ◽

Jean Rommelaere

Keyword(s):

Clinical Trials ◽

Cell Death ◽

Immune System ◽

Tumor Microenvironment ◽

Immune Suppression ◽

Molecular Mechanisms ◽

Clinical Development ◽

Host Immune System ◽

Tumor Cell Death ◽

Immunogenic Tumor Cell

Rodent protoparvoviruses (PVs), parvovirus H-1 (H-1PV) in particular, are naturally endowed with oncolytic properties. While being historically described as agents that selectively replicate in and kill cancer cells, recent yet growing evidence demonstrates that these viruses are able to reverse tumor-driven immune suppression through induction of immunogenic tumor cell death, and the establishment of antitumorigenic, proinflammatory milieu within the tumor microenvironment. This review summarizes the most important preclinical proofs of the interplay and the cooperation between PVs and the host immune system. The molecular mechanisms of PV-induced immunostimulation are also discussed. Furthermore, initial encouraging in-human observations from clinical trials and compassionate virus uses are presented, and speak in favor of further H-1PV clinical development as partner drug in combined immunotherapeutic protocols.

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Immune System Modulation and Viral Persistence in Bats: Understanding Viral Spillover

Viruses ◽

10.3390/v11020192 ◽

2019 ◽

Vol 11 (2) ◽

pp. 192 ◽

Cited By ~ 17

Author(s):

Sonu Subudhi ◽

Noreen Rapin ◽

Vikram Misra

Keyword(s):

Viral Load ◽

Immune System ◽

Virus Replication ◽

Defense Mechanisms ◽

Molecular Mechanisms ◽

Viral Persistence ◽

Latently Infected ◽

Unique Nature ◽

Immune System Modulation ◽

Perfect Storm

Bats harbor a myriad of viruses and some of these viruses may have spilled over to other species including humans. Spillover events are rare and several factors must align to create the “perfect storm” that would ultimately lead to a spillover. One of these factors is the increased shedding of virus by bats. Several studies have indicated that bats have unique defense mechanisms that allow them to be persistently or latently infected with viruses. Factors leading to an increase in the viral load of persistently infected bats would facilitate shedding of virus. This article reviews the unique nature of bat immune defenses that regulate virus replication and the various molecular mechanisms that play a role in altering the balanced bat–virus relationship.

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UJI IMUNOSTIMULATOR DARI KOMBINASI EKSTRAK ETANOL HERBA BINARA (ARTEMISIA VULGARIS LINN) DAN EKSTRAK ETANOL DAUN PUCUK MERAH (SYZYGIUM OLEANA) DENGAN METODE HIPERSENSITIVITAS TIPE LAMBAT PADA TIKUS JANTAN

Jurnal Penelitian Farmasi & Herbal ◽

10.36656/jpfh.v1i2.105 ◽

2019 ◽

Vol 1 (2) ◽

pp. 22-26

Author(s):

Romauli Anna Teresia Marbun ◽

Aminah Syarifuddin ◽

Montysory Silalahi ◽

Radika Bella Fista Ginting

Keyword(s):

Antioxidant Activity ◽

Immune System ◽

Secondary Metabolites ◽

Ethanol Extract ◽

Positive Control ◽

Artemisia Vulgaris ◽

Chemical Screening ◽

Chemical Content ◽

High Antioxidant Activity ◽

New Treatments

Diseases mediated by the immune system are difficult problems to treat such as human immunodeficiency virus (HIV) and other lethal viruses. Infections that occur in normal people are generally brief and rarely leave permanent damage. Treatment of this disease requires an aggressive and innovative approach to the development of new treatments so that it requires the role of immunomodulators to improve the immune system. A substance that acts as an enhancer or immune enhancer can be obtained by using herbs that are efficacious as immunostimulants. One of the herbs used is herbal binara (Artemisia vulgaris L) which has been studied as a potential immunomodulator with high antioxidant activity. Previous research also stated that red shoots (Syzygium oleana) were studied as potential immunomodulators with high antioxidant activity. Several other species such as Syzygium samarangense have 16 flavonoida compounds which show pharmacological immunological activity. The purpose of this study was to determine the content of secondary metabolites of ethanol extract of herbal binara (Artemisia vulgaris L.) with red shoots (Syzygium oleana) and to determine the best dose of extract from the ethanol extract of herbal binara (Artemisia vulgaris L.) with red shoots (Syzygium oleana) can reduce the volume of swelling of mouse feet. Examination of the chemical content of secondary metabolites from the ethanol extract of herbal binara (Artemisia vulgaris L.) with red shoots (Syzygium oleana) is carried out by chemical screening and characterization of simplicia and extract. The method used is the slow type hypersensitivity method. In this test the independent variable is the secondary metabolite of ethanol extract of herb binara (Artemisia vulgaris L.) with red shoots (Syzygium oleana) with four concentrations (50, 100, 200 and 400 mg / kgBB). The positive control used by Stimuno dose is 32.5 mg / kgBB

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New Trends in Anti-Cancer Therapy: Combining Conventional Chemotherapeutics with Novel Immunomodulators

Current Medicinal Chemistry ◽

10.2174/0929867324666170830094922 ◽

2018 ◽

Vol 25 (36) ◽

pp. 4758-4784 ◽

Cited By ~ 8

Author(s):

Amy L. Wilson ◽

Magdalena Plebanski ◽

Andrew N. Stephens

Keyword(s):

Clinical Trials ◽

Cell Death ◽

Immune System ◽

Cancer Therapy ◽

Immune Cell ◽

Cytotoxic T Lymphocyte ◽

Tumour Microenvironment ◽

Immune Checkpoints ◽

Tumour Regression ◽

Cell Trafficking

Cancer is one of the leading causes of death worldwide, and current research has focused on the discovery of novel approaches to effectively treat this disease. Recently, a considerable number of clinical trials have demonstrated the success of immunomodulatory therapies for the treatment of cancer. Monoclonal antibodies can target components of the immune system to either i) agonise co-stimulatory molecules, such as CD137, OX40 and CD40; or ii) inhibit immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and its corresponding ligand PD-L1. Although tumour regression is the outcome for some patients following immunotherapy, many patients still do not respond. Furthermore, chemotherapy has been the standard of care for most cancers, but the immunomodulatory capacity of these drugs has only recently been uncovered. The ability of chemotherapy to modulate the immune system through a variety of mechanisms, including immunogenic cell death (ICD), increased antigen presentation and depletion of regulatory immune cells, highlights the potential for synergism between conventional chemotherapy and novel immunotherapy. In addition, recent pre-clinical trials indicate dipeptidyl peptidase (DPP) enzyme inhibition, an enzyme that can regulate immune cell trafficking to the tumour microenvironment, as a novel cancer therapy. The present review focuses on the current immunological approaches for the treatment of cancer, and summarizes clinical trials in the field of immunotherapy as a single treatment and in combination with chemotherapy.

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The Mechanisms Behind the Biological Activity of Flavonoids

Current Medicinal Chemistry ◽

10.2174/0929867325666180706104829 ◽

2019 ◽

Vol 26 (39) ◽

pp. 6976-6990 ◽

Cited By ~ 12

Author(s):

Ana María González-Paramás ◽

Begoña Ayuda-Durán ◽

Sofía Martínez ◽

Susana González-Manzano ◽

Celestino Santos-Buelga

Keyword(s):

Gene Expression ◽

Biological Activity ◽

Phenolic Compounds ◽

Intracellular Signaling ◽

Molecular Mechanisms ◽

Radical Scavenging ◽

Model Organism ◽

Stress Theory ◽

Radical Scavenging Properties

: Flavonoids are phenolic compounds widely distributed in the human diet. Their intake has been associated with a decreased risk of different diseases such as cancer, immune dysfunction or coronary heart disease. However, the knowledge about the mechanisms behind their in vivo activity is limited and still under discussion. For years, their bioactivity was associated with the direct antioxidant and radical scavenging properties of phenolic compounds, but nowadays this assumption is unlikely to explain their putative health effects, or at least to be the only explanation for them. New hypotheses about possible mechanisms have been postulated, including the influence of the interaction of polyphenols and gut microbiota and also the possibility that flavonoids or their metabolites could modify gene expression or act as potential modulators of intracellular signaling cascades. This paper reviews all these topics, from the classical view as antioxidants in the context of the Oxidative Stress theory to the most recent tendencies related with the modulation of redox signaling pathways, modification of gene expression or interactions with the intestinal microbiota. The use of C. elegans as a model organism for the study of the molecular mechanisms involved in biological activity of flavonoids is also discussed.

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Antibody Therapy for the Control of Viral Diseases: An Update

Current Pharmaceutical Biotechnology ◽

10.2174/1389201020666190809112704 ◽

2019 ◽

Vol 20 (13) ◽

pp. 1108-1121 ◽

Cited By ~ 7

Author(s):

Miriam Dibo ◽

Eduardo C. Battocchio ◽

Lucas M. dos Santos Souza ◽

Matheus D. Veloso da Silva ◽

Bruna K. Banin-Hirata ◽

...

Keyword(s):

Clinical Trials ◽

Monoclonal Antibodies ◽

Viral Antigen ◽

Viral Infections ◽

Antibody Therapy ◽

Therapeutic Strategies ◽

Viral Diseases ◽

Specific Antibodies ◽

The Status ◽

Epidemiological Impact

The epidemiological impact of viral diseases, combined with the emergence and reemergence of some viruses, and the difficulties in identifying effective therapies, have encouraged several studies to develop new therapeutic strategies for viral infections. In this context, the use of immunotherapy for the treatment of viral diseases is increasing. One of the strategies of immunotherapy is the use of antibodies, particularly the monoclonal antibodies (mAbs) and multi-specific antibodies, which bind directly to the viral antigen and bring about activation of the immune system. With current advancements in science and technology, several such antibodies are being tested, and some are already approved and are undergoing clinical trials. The present work aims to review the status of mAb development for the treatment of viral diseases.

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The Immune System Regulation in Sepsis: From Innate to Adaptive

Current Protein and Peptide Science ◽

10.2174/1389203720666190305164128 ◽

2019 ◽

Vol 20 (8) ◽

pp. 799-816 ◽

Cited By ~ 6

Author(s):

Yue Qiu ◽

Guo-wei Tu ◽

Min-jie Ju ◽

Cheng Yang ◽

Zhe Luo

Keyword(s):

Clinical Trials ◽

Immune System ◽

Systemic Inflammatory Response Syndrome ◽

Inflammatory Response ◽

Immune Cells ◽

Current Knowledge ◽

Systemic Inflammatory Response ◽

Immune System Regulation

Sepsis, which is a highly heterogeneous syndrome, can result in death as a consequence of a systemic inflammatory response syndrome. The activation and regulation of the immune system play a key role in the initiation, development and prognosis of sepsis. Due to the different periods of sepsis when the objects investigated were incorporated, clinical trials often exhibit negative or even contrary results. Thus, in this review we aim to sort out the current knowledge in how immune cells play a role during sepsis.

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Potential Therapeutic Targets of Curcumin, Most Abundant Active Compound of Turmeric Spice: Role in the Management of Various Types of Cancer

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892815999201102214602 ◽

2020 ◽

Vol 15 ◽

Author(s):

Saleh A. Almatroodi ◽

Mansoor Ali Syed ◽

Arshad Husain Rahmani

Keyword(s):

Clinical Trials ◽

Cancer Cells ◽

Active Compound ◽

Molecular Mechanisms ◽

Human Subjects ◽

Cell Signalling ◽

Chemopreventive Agents ◽

Signalling Molecules ◽

Cancer Management ◽

Induced Apoptosis

Background:: Curcumin, an active compound of turmeric spice is one of the most-studies natural compounds and have been widely recognized as chemopreventive agents. Several molecular mechanisms have been proven, curcumin and its analogs play a role in cancer prevention through modulating various cell signaling pathways as well as inhibition of carcinogenesis process. Objective:: To study the potential role of curcumin in the management of various types of cancer through modulating cell signalling molecules based on available literature and recent patents. Methods:: A wide-ranging literature survey was performed based on Scopus, PubMed, PubMed central and Google scholar for the implication of curcumin in cancer management along with special emphasis on human clinical trials. Moreover, patents were searched through www.google.com/patents, www.freepatentsonline.com and www.freshpatents.com. Result:: Recent studies based on cancer cells have proven that curcumin have potential effects against cancer cells, prevent the growth of cancer and act as cancer therapeutic agents. Besides, curcumin exerted anticancer effects through inducing apoptosis, activating tumor suppressor genes, cell cycle arrest, inhibiting tumor angiogenesis, initiation, promotion and progression stages of tumor. It was established that co-treatment of curcumin and anti-cancer drugs could induce apoptosis and also play a significant role in the suppression of the invasion and metastasis of cancer cells. Conclusion:: Accumulating evidences suggest that curcumin has potentiality to inhibit cancer growth, induced apoptosis and modulate various cell signalling pathways molecules. Well-designed clinical trials of curcumin based on human subjects are still needed to establish the bioavailability, mechanism of action, efficacy and safe dose in the management of various cancers.

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PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects

International Journal of Molecular Sciences ◽

10.3390/ijms22073464 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3464

Author(s):

Rosalin Mishra ◽

Hima Patel ◽

Samar Alanazi ◽

Mary Kate Kilroy ◽

Joan T. Garrett

Keyword(s):

Clinical Trials ◽

Intracellular Signaling ◽

Pi3k Pathway ◽

Combination Therapies ◽

Intracellular Signaling Pathway ◽

Pi3k Inhibitors ◽

Promising Therapeutic Target ◽

Cancer Cell Survival ◽

Current Therapies ◽

Cancer Types

The phospatidylinositol-3 kinase (PI3K) pathway is a crucial intracellular signaling pathway which is mutated or amplified in a wide variety of cancers including breast, gastric, ovarian, colorectal, prostate, glioblastoma and endometrial cancers. PI3K signaling plays an important role in cancer cell survival, angiogenesis and metastasis, making it a promising therapeutic target. There are several ongoing and completed clinical trials involving PI3K inhibitors (pan, isoform-specific and dual PI3K/mTOR) with the goal to find efficient PI3K inhibitors that could overcome resistance to current therapies. This review focuses on the current landscape of various PI3K inhibitors either as monotherapy or in combination therapies and the treatment outcomes involved in various phases of clinical trials in different cancer types. There is a discussion of the drug-related toxicities, challenges associated with these PI3K inhibitors and the adverse events leading to treatment failure. In addition, novel PI3K drugs that have potential to be translated in the clinic are highlighted.

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Conventional and Organic Honeys as a Source of Water- and Ethanol Soluble Molecules with Nutritional and Antioxidant Characteristics

Molecules ◽

10.3390/molecules26123746 ◽

2021 ◽

Vol 26 (12) ◽

pp. 3746

Author(s):

Magdalena Polak-Śliwińska ◽

Małgorzata Tańska

Keyword(s):

Antioxidant Activity ◽

Immune System ◽

Vitamin C ◽

Geographical Area ◽

Production Method ◽

Climatic Conditions ◽

Organic Production ◽

Organoleptic Characteristics ◽

Nutritional Characteristics ◽

The Impact

The benefits of natural honeybee products (e.g., honey, royal jelly, beeswax, propolis, beevenom and pollen) to the immune system are remarkable, and many of them are involved in the induction of antibody production, maturation of immune cells and stimulation of the immune system. The type of plants in the geographical area, climatic conditions and production method have a significantly influence on the nutritional quality of honey. However, this variability can influence consumer liking by the sensory attributes of the product. The aim of this work was to compare the most popular honeys from Poland in terms of nutritional value, organoleptic properties and antioxidant activity. In the study, five varieties of honey (honeydew, forest, buckwheat, linden and dandelion) from conventional and organic production methods were tested. The nutritional characteristics of honey samples included acidity, content of water, sugars, vitamin C, HMF and phenolics (total and flavonoids), while honey color, taste, aroma and consistency were investigated in the organoleptic characteristics. The antioxidant activity was determined in water- and ethanol-soluble honey extracts using DPPH and ORAC tests. The results showed that organoleptic and nutritional characteristics of popular Polish honeys differ significantly in relation to plant source and production method. The significant effect of honey variety on the content of HMF, saccharose and phenolics, as well as acidity and antioxidant capacity were noted. The impact of variety and variety × production method interaction was significant in the case of the content of vitamin C, glucose and fructose. A visible difference of buckwheat and forest honeys from other samples was observed. The highest content of total phenolics with antioxidant activity based on the SET mechanism was found in buckwheat honeys, while forest honeys were richer in flavonoids.

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