Molecular Mechanisms of Curcumin in COVID-19 Treatment and Prevention: A Global Health Perspective

Turmeric (Curcuma Longa) has a near 4000-year history of extensive medical use in South Asia. Its main physiologically active phytochemical is curcumin (diferuloylmethane), derived from the rhizome of turmeric. Curcumin is a hydrophobic polyphenol with a diketone moiety connecting two phenoxy rings. It is widely available, and exerts systemic and pleiotropic effects via several key mechanisms. Most famously, it is known to inhibit pro-inflammatory pathways such as PI3k/akt/NF-kB activation. It is also a potent antioxidant and free radical scavenger via a sequential proton loss electron transfer mechanism in ionizing solvents due to its extended conjugating ability across the entire molecule, and its ability to induce NRF-2. It has been implicated in the treatment of diseases ranging from asthma to various cancers, and is also a broad spectrum anti-microbial. COVID-19 is a novel beta-coronavirus that was declared a pandemic by the WHO in March, 2020. It is primarily a respiratory disorder, but it can spread hematogenously and effect many other organs such as the heart, nervous system, and kidneys. There is a significant intersection between the clinical manifestations of COVID-19 and curcumin’s therapeutic effects. In addition, curcumin has been shown to inhibit initial viral infectivity. Thus, there is potential for curcumin to safely both prevent and treat COVID-19 infection across the globe.

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Betanin: a promising molecule for biomedical applications

Biointerface Research in Applied Chemistry ◽

10.33263/briac103.392399 ◽

2020 ◽

Vol 10 (3) ◽

pp. 5392-5399

Keyword(s):

Positive Impact ◽

Pharmaceutical Products ◽

Free Radical Scavenger ◽

Biologically Active ◽

New Drugs ◽

Radical Scavenger ◽

Therapeutic Effects ◽

Pharmacological Properties ◽

Natural Colorant ◽

Anti Oxidant

Plants with medicinal properties possess beneficial influences on health and disease. Different plant parts and extracts carry valuable active ingredients with pharmacological properties that lead to developing new drugs. Terminalia bellirica is among those plants that have been formulated as pharmaceutical products. This is attributed to its biologically active phenolics and tannins exhibiting analgesic, anti-hypertensive, anti-microbial, anti-diabetic, anti-oxidant, as well as, other pharmacological properties. Beetroot has been shown to be rich in nitrates with a positive impact on the cardiovascular system. Beetroot contains a number of useful ingredients as the free-radical scavenger ascorbic acid, the anti-inflammatory flavonoids and the anti-oxidant carotenoids. Moreover, beetroot is rich in the natural colorant betalains that are further classified into betacyanins and betaxanthins. Betanin, is one of the major constituents of beetroots that have been postulated to possess significant beneficial therapeutic effects in a number of conditions and diseases. However, several studies have demonstrated the relatively poor bioavailability of betanin upon oral administration. In the current review we aim to highlight some of the latest researches dealing with the therapeutic properties of betanin in different disease conditions, the possible mechanistic pathways beyond such beneficial effects and plausible strategies capable of enhancing its stability and bioavailability.

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Traumatic Brain Injury: Oxidative Stress and Novel Anti-Oxidants Such as Mitoquinone and Edaravone

Antioxidants ◽

10.3390/antiox9100943 ◽

2020 ◽

Vol 9 (10) ◽

pp. 943 ◽

Cited By ~ 1

Author(s):

Helene Ismail ◽

Zaynab Shakkour ◽

Maha Tabet ◽

Samar Abdelhady ◽

Abir Kobaisi ◽

...

Keyword(s):

Oxidative Stress ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Neuroprotective Effect ◽

Treatment Options ◽

Free Radical Scavenger ◽

Health Concern ◽

Radical Scavenger ◽

History Of ◽

Ionic Imbalance

Traumatic brain injury (TBI) is a major health concern worldwide and is classified based on severity into mild, moderate, and severe. The mechanical injury in TBI leads to a metabolic and ionic imbalance, which eventually leads to excessive production of reactive oxygen species (ROS) and a state of oxidative stress. To date, no drug has been approved by the food and drug administration (FDA) for the treatment of TBI. Nevertheless, it is thought that targeting the pathology mechanisms would alleviate the consequences of TBI. For that purpose, antioxidants have been considered as treatment options in TBI and were shown to have a neuroprotective effect. In this review, we will discuss oxidative stress in TBI, the history of antioxidant utilization in the treatment of TBI, and we will focus on two novel antioxidants, mitoquinone (MitoQ) and edaravone. MitoQ can cross the blood brain barrier and cellular membranes to accumulate in the mitochondria and is thought to activate the Nrf2/ARE pathway leading to an increase in the expression of antioxidant enzymes. Edaravone is a free radical scavenger that leads to the mitigation of damage resulting from oxidative stress with a possible association to the activation of the Nrf2/ARE pathway as well.

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Pleiotropic roles of melatonin against oxidative stress mediated tissue injury in the gastrointestinal tract: An overview

Melatonin Research ◽

10.32794/mr11250027 ◽

2019 ◽

Vol 2 (2) ◽

pp. 158-184 ◽

Cited By ~ 4

Author(s):

Palash K Pal ◽

Bharati Bhattacharjee ◽

Aindrila Chattopadhyay ◽

Debasish Bandyopadhyay

Keyword(s):

Oxidative Stress ◽

Molecular Mechanisms ◽

Clinical Symptoms ◽

Tissue Injury ◽

Ischemia Reperfusion ◽

Antioxidant Properties ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Gi Tract ◽

Pathological Conditions

The excessive production of free radicals and/or reactive oxygen species (ROS) in gastrointestinal (GI) tract leads to oxidative damages in GI tissues with development of varied pathological conditions and clinical symptoms. Many endogenous as well as exogenous factors are involved in such pathogenesis, herein, focus was given to the factors of metal toxicity, non-steroidal anti-inflammatory drugs (NSAIDs), ischemia-reperfusion, consumption of high fat diet and alcohol, and different pathological conditions and diseases. Since ROS is more or less involved in the GI damages caused by these factors, therefore attempts have been made to develop appropriate therapeutic agents that possess antioxidant properties. Being a potent antioxidant and free radical scavenger, melatonin was suggested as a potent therapeutic answer to these GI damages. The discovery of different binding sites and receptors of melatonin in the GI tissues further proves its local actions to protect these tissues from oxidative stress. In the review, we attempt to try our best to summarize the current developments regarding the GI injuries caused by oxidative stress and the potential beneficial effects of melatonin on these injuries. The important molecular mechanisms associated with these changes were also highlighted in the discussion. We hope that this review will provide valuable information to consider melatonin as a suitable molecule used for GI tract protection.

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Associative relationship between atopy, HLA complex genes and other genes

Rossiiskii Allergologicheskii ZHurnal ◽

10.36691/rja1206 ◽

2019 ◽

Vol 16 (3) ◽

pp. 5-25

Author(s):

N G Astafyeva ◽

B A Shamgunova ◽

D Yu Kobzev ◽

I Ae Michailova

Keyword(s):

Molecular Mechanisms ◽

Complex Structure ◽

Clinical Manifestations ◽

Current Data ◽

Genetic Determinants ◽

Genetic Characteristics ◽

Hla Genes ◽

Histocompatibility Complex ◽

History Of

This review presents current data on the associative relationships of genes of the major histocompatibility complex (HLA) and other genes with atopy. Despite the long history of studying the role of HLA class genes in atopy and the introduction of modern technologies and methods, many unresolved issues remain, including the difficulties caused by the heterogeneity of the human population, the complex structure and disequilibrium of linkage between different HLA genes. Although phenotypic heterogeneity is considered as the main limitation in understanding the genetic determinants of atopy, only a few studies have examined the relationships of its typical clinical manifestations induced by aeroallergens with certain HLA genes. The identified molecular mechanisms and genetic characteristics open up the possibility of using new therapeutic targets and modifying existing drugs.

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Edaravone Ameliorates Depressive and Anxiety-like Behaviors via Sirt1/Nrf2/HO-1/Gpx4 Pathway

10.21203/rs.3.rs-850484/v1 ◽

2021 ◽

Author(s):

Ruozhi Dang ◽

Mingyang Wang ◽

Xinhui Li ◽

Haiyang Wang ◽

Lanxiang Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Molecular Mechanisms ◽

Biological Activities ◽

Forced Swim Test ◽

Preference Test ◽

Antidepressant Activity ◽

Tail Suspension Test ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Nissl Staining

Abstract Background: The inflammation and oxidative stress (OS) have been considered crucial components of the pathogenesis of depression. Edaravone (EDA), a free radical scavenger, processes strong biological activities including antioxidant, anti-inflammatory and neuroprotective properties. However, its role and potential molecular mechanisms in depression remain unclear. The present study aimed to investigate the antidepressant activity of EDA and its underlying mechanisms.Methods: A chronic social defeat stress (CSDS) depression model was performed to explore whether EDA could produce antidepressant effects. C57BL/6J mice were intraperitoneally injected with EDA or Vehicle daily for 10 days. Behaviors tests were then carried out to examine depressive, anxiety-like and cognitive behaviors including social interaction (SI) test, sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM), novel object recognition (NOR), tail suspension test (TST) and forced swim test (FST). Hippocampal and medial prefrontal cortex (mPFC) tissues were collected for Nissl staining, immunofluorescence, targeted energy metabolomics analysis, measurement of MDA, SOD, GSH and transmission electron microscopy (TEM). Western blotting (WB) and quantitative real time polymerase chain reaction (qRT-PCR) detected the Sirt1/Nrf2/HO-1/Gpx4 signaling pathway. Knockdown experiments were performed to determine the effects of Gpx4 on CSDS mice with EDA treatment by an adeno-associated virus (AAV) vector containing miRNAi(GPX4)-EGFP infusion.Results: The administrated of EDA dramatically ameliorated CSDS-induced depressive and anxiety-like behaviors. Additionally, EDA notably attenuated neuronal loss, microglial activation, astrocyte dysfunction, oxidative stress damage and energy metabolism in the hippocampus (Hip) and mPFC of CSDS-induced mice. Further examination indicated that the application of EDA after the CSDS model significantly increased the protein expressions of Sirt1, Nrf2, HO-1 and Gpx4 in the Hip. In addition, Gpx4 knockdown in CSDS mice abolished EDA-generated efficacy on depressive and anxiety-like behaviors.Conclusion: These findings suggest that EDA possesses potent antidepressant and anxiolytic properties through Sirt1/Nrf2/HO-1/Gpx4 axis and Gpx4-mediated ferroptosis may play a key role in this effect.

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Natural Products as Anticancer Agents

Current Drug Targets ◽

10.2174/1389450121999201230204526 ◽

2020 ◽

Vol 22 ◽

Author(s):

Ruby Varghese ◽

Yogesh Bharat. Dalvi

Keyword(s):

Natural Products ◽

Anticancer Agents ◽

Cancer Metastasis ◽

Kinase Inhibitor ◽

Curcuma Longa ◽

Aloe Vera ◽

Angiogenesis Inhibitor ◽

Cancer Therapeutics ◽

Free Radical Scavenger ◽

Radical Scavenger

Abstract:: Medicinal plants and mushrooms have alwaysfascinated the world as an attractive source of natural compounds for cancer therapy. From ancient times, they have been valued as gourmet food and folk medicine in Oriental practice. For over 40 years, world has witnessed the overwhelming interest of western scientific fraternity in pharmaceutical potential of natural products in combating cancer. The plants and mushrooms credited with success against angiogenesis and cancer metastasis belong to certain Plants including Catharanthus roseus, Aloe Vera,Annona muricata,Curcuma longa, Withania somnifera, and Berberis and mushrooms such as Agaricus,Antrodia,Ganoderma,Grifolafrondosa,Hericiumerinaceus,Phel-linuslinteus, and Trametesversicolor /Coriolusversicolor. The anti-cancer compounds play a pivotal role as free radical scavenger and reactive oxygen species inducer, mitotic spindle kinase inhibitor, anti-mitotic, angiogenesis inhibitor, topoi-somerase inhibitor, apoptosis inducers, and eventually checking cancer invasion, migration and proliferation. The present review updates and focuses on the recent findings of the pharmacologically potential bioactive compounds, their anti-tumor potential, and underlying mechanism of preventing cancer metastasis and angiogenesisin order to raise knowledge for fur-ther investigations to develop cancer therapeutics with no adverse side effects The mounting experimental evidences at pre-clinical and clinical levels from various research groups across the globe, regarding prevention of cancer metastasis by natural products unarguably make it a fast-track research area worth mass attention.

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The Potential Use of Melatonin for Preventing Cisplatin Ototoxicity: An Insight for a Clinical Approach

Advances in Otolaryngology ◽

10.1155/2014/185617 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8

Author(s):

Juliana Gusmão de Araujo ◽

André Luiz Lopes Sampaio ◽

Alessandra Ramos Venosa ◽

Carlos Augusto Costa Pires de Oliveira

Keyword(s):

Noise Exposure ◽

Therapeutic Option ◽

Organ Of Corti ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Clinical Approach ◽

Cumulative Number ◽

Oxygen Species ◽

History Of ◽

Potential Use

Cisplatin, one of the most effective and potent anticancer drugs, is used in the treatment of a wide variety of both pediatric and adult malignancies. However, the chemotherapeutic use of cisplatin is limited by its serious side effects, such as nephrotoxicity and ototoxicity. Ototoxicity produced by cisplatin is usually persistent, depending on the age of the patient, the cumulative number of doses, the number of chemotherapy cycles, the history of noise exposure, and deteriorating renal function. The mechanism of the ototoxicity caused by cisplatin is based on the generation of reactive oxygen species, which interfere with the antioxidant protection of the organ of Corti. Thus, protecting the cochlea with antioxidants ameliorates ototoxicity from cisplatin. In this context, melatonin appears as a therapeutic option for preventing the ototoxic effects of cisplatin, since the research in the last decade has proven its ability to be both a direct free radical scavenger and indirect antioxidant. In this sense, some of the evidence suggesting that melatonin is efficient for combating cisplatin-induced ototoxicity is summarized and discussed in this paper.

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Physiological and Therapeutical Roles of Ginger and Turmeric on Endocrine Functions

The American Journal of Chinese Medicine ◽

10.1142/s0192415x11008762 ◽

2011 ◽

Vol 39 (02) ◽

pp. 215-231 ◽

Cited By ~ 21

Author(s):

Ebtesam A. Al-Suhaimi ◽

Noorah A. Al-Riziza ◽

Reham A. Al-Essa

Keyword(s):

Molecular Mechanisms ◽

Hormone Receptors ◽

Potent Inhibitor ◽

Curcuma Longa ◽

Zingiber Officinale ◽

Target Cells ◽

Signal Pathways ◽

Endocrine Gland ◽

Therapeutic Effects ◽

Natural Agents

The natural product ginger (Zingiber officinale) has active constituents gingerol, Shogaol and Zerumbone, while turmeric (Curcuma longa) contains three active major curcuminoids, namely, curcumin, demethoxycurcumin, and bisdemethoxycurcumin. They have the same scientific classification and are reported to have anti-inflammatory and many therapeutic effects. This article reviews the physiological and therapeutic effects of ginger and turmeric on some endocrine gland functions, and signal pathways involved to mediate their actions. With some systems and adipose tissue, ginger and turmeric exert their actions through some/all of the following signals or molecular mechanisms: (1) through reduction of high levels of some hormones (as: T4, leptin) or interaction with hormone receptors; (2) by inhibition of cytokines/adipokine expression; (3) acting as a potent inhibitor of reactive oxygen species (ROS)-generating enzymes, which play an essential role between inflammation and progression of diseases; (4) mediation of their effects through the inhibition of signaling transcription factors; and/or (5) decrease the proliferative potent by down-regulation of antiapoptotic genes, which may suppress tumor promotion by blocking signal transduction pathways in the target cells. These multiple mechanisms of protection against inflammation and oxidative damage make ginger and curcumin particularly promising natural agents in fighting the ravages of aging and degenerative diseases, and need to be paid more attention by studies.

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Protective Effect of Edaravone on Glutamate-Induced Neurotoxicity in Spiral Ganglion Neurons

Neural Plasticity ◽

10.1155/2016/4034218 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Xiaohui Bai ◽

Chi Zhang ◽

Aiping Chen ◽

Wenwen Liu ◽

Jianfeng Li ◽

...

Keyword(s):

Cell Death ◽

Cell Damage ◽

Spiral Ganglion ◽

Free Radical Scavenger ◽

Blue Staining ◽

Radical Scavenger ◽

Auditory Information ◽

Therapeutic Effects ◽

Spiral Ganglion Neurons ◽

Ganglion Neurons

Glutamate is an important excitatory neurotransmitter in mammalian brains, but excessive amount of glutamate can cause “excitotoxicity” and lead to neuronal death. As bipolar neurons, spiral ganglion neurons (SGNs) function as a “bridge” in transmitting auditory information from the ear to the brain and can be damaged by excessive glutamate which results in sensorineural hearing loss. In this study, edaravone, a free radical scavenger, elicited both preventative and therapeutic effects on SGNs against glutamate-induced cell damage that was tested by MTT assay and trypan blue staining. Ho.33342 and PI double staining revealed that apoptosis as well as necrosis took place during glutamate treatment, and apoptosis was the main type of cell death. Oxidative stress played an important role in glutamate-induced cell damage but pretreatment with edaravone alleviated cell death. Results of western blot demonstrated that mechanisms underlying the toxicity of glutamate and the protection of edaravone were related to the PI3K pathway and Bcl-2 protein family.

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Alkaptonuria – Many questions answered, further challenges beckon

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/0004563219879957 ◽

2019 ◽

Vol 57 (2) ◽

pp. 106-120

Author(s):

AS Davison ◽

AT Hughes ◽

AM Milan ◽

N Sireau ◽

JA Gallagher ◽

...

Keyword(s):

Molecular Mechanisms ◽

Human Subjects ◽

Clinical Manifestations ◽

Homogentisic Acid ◽

Common Disease ◽

Clinical Complications ◽

Disease Modifying Therapy ◽

Treatment Measures ◽

History Of ◽

Collagenous Tissues

Alkaptonuria is an iconic rare inherited inborn error of metabolism affecting the tyrosine metabolic pathway, resulting in the accumulation of homogentisic acid in the circulation, and significant excretion in urine. Dating as far back as 1500 BC in the Egyptian mummy Harwa, homogentisic acid was shown to be central to the pathophysiology of alkaptonuria through its deposition in collagenous tissues in a process termed ochronosis. Clinical manifestations occurring as a consequence of this are typically observed from the third decade of life, are lifelong and significantly affect the quality of life. In large supportive and palliative treatment measures are available to patients, including analgesia, physiotherapy and joint replacement. Studying the natural history of alkaptonuria, in a murine model and human subjects, has provided key insights into the biochemical and molecular mechanisms underlying the pathophysiology associated with the disease, and has enabled a better understanding of the common disease osteoarthritis. In the last decade, a major focus has been on an unlicensed disease-modifying therapy called nitisinone. This has been shown to be highly efficacious in reducing homogentisic acid, and it is hoped this will halt ochronosis, thus limiting the clinical complications associated with the disease. A well-documented metabolic consequence of nitisinone therapy is hypertyrosinaemia, the clinical implications of which are uncertain. Recent metabolomic studies have helped understand the wider metabolic consequences of nitisinone therapy.

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