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Article ; Online: NF-κB signalling as a pharmacological target in COVID-19: potential roles for IKKβ inhibitors.

Kandasamy, Mahesh

Naunyn-Schmiedeberg's archives of pharmacology

2021 Volume 394, Issue 3, Page(s) 561–567

Abstract: Coronavirus disease 2019 (COVID-19) has been characterized by lymphopenia as well as a proinflammatory cytokine storm, which are responsible for the poor prognosis and multiorgan defects. The transcription factor nuclear factor-κB (NF-κB) modulates the ... ...

Abstract	Coronavirus disease 2019 (COVID-19) has been characterized by lymphopenia as well as a proinflammatory cytokine storm, which are responsible for the poor prognosis and multiorgan defects. The transcription factor nuclear factor-κB (NF-κB) modulates the functions of the immune cells and alters the gene expression profile of different cytokines in response to various pathogenic stimuli, while many proinflammatory factors have been known to induce NF-κB signalling cascade. Besides, NF-κB has been known to potentiate the production of reactive oxygen species (ROS) leading to apoptosis in various tissues in many diseases and viral infections. Though the reports on the involvement of the NF-κB signalling pathway in COVID-19 are limited, the therapeutic benefits of NF-κB inhibitors including dexamethasone, a synthetic form of glucocorticoid, have increasingly been realized. Considering the fact, the abnormal activation of the NF-κB resulting from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection might be associated with the pathogenic profile of immune cells, cytokine storm and multiorgan defects. Thus, the pharmacological inactivation of the NF-κB signalling pathway can strongly represent a potential therapeutic target to treat the symptomatology of COVID-19. This article signifies pharmacological blockade of the phosphorylation of inhibitor of nuclear factor kappa B kinase subunit beta (IKKβ), a key downstream effector of NF-κB signalling, for a therapeutic consideration to attenuate COVID-19.
MeSH term(s)	Animals ; COVID-19/drug therapy ; COVID-19/epidemiology ; COVID-19/metabolism ; Cytokine Release Syndrome/drug therapy ; Cytokine Release Syndrome/epidemiology ; Cytokine Release Syndrome/metabolism ; Drug Delivery Systems/trends ; Heterocyclic Compounds, 3-Ring/administration & dosage ; Humans ; I-kappa B Kinase/antagonists & inhibitors ; I-kappa B Kinase/metabolism ; Lymphopenia/drug therapy ; Lymphopenia/epidemiology ; Lymphopenia/metabolism ; NF-kappa B/antagonists & inhibitors ; NF-kappa B/metabolism ; Nitriles/administration & dosage ; Pyridines/administration & dosage ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Sulfones/administration & dosage
Chemical Substances	3-(4-methylphenylsulfonyl)-2-propenenitrile ; Heterocyclic Compounds, 3-Ring ; NF-kappa B ; Nitriles ; PS1145 ; Pyridines ; Sulfones ; I-kappa B Kinase (EC 2.7.11.10) ; IKBKB protein, human (EC 2.7.11.10)
Language	English
Publishing date	2021-01-04
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	121471-8
ISSN	1432-1912 ; 0028-1298
ISSN (online)	1432-1912
ISSN	0028-1298
DOI	10.1007/s00210-020-02035-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Perspectives for the use of therapeutic Botulinum toxin as a multifaceted candidate drug to attenuate COVID-19.

Kandasamy, Mahesh

Medicine in drug discovery

2020 Volume 6, Page(s) 100042

Abstract: The recent outbreak of coronavirus disease (COVID-19) resulting from a distinctive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to evolve in many countries and pose life-threatening clinical issues to global public health. While ...

Abstract	The recent outbreak of coronavirus disease (COVID-19) resulting from a distinctive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to evolve in many countries and pose life-threatening clinical issues to global public health. While the lungs are the primary target for the SARS-CoV-2-mediated pathological consequence, the virus appears to invade the brain and cause unpredicted neurological deficits. In the later stage, COVID-19 can progress to pneumonia, acute respiratory failure, neurodegeneration and multi-organ dysfunctions leading to death. Though a significant portion of individuals with COVID-19 has been recovering from clinical symptoms, the pathological impact of the SARS-CoV-2 infection on the structural and functional properties of the lungs, heart, brain and other organs at the post-recovery state remains unknown. Presently, there is an urgent need for a remedial measure to combat this devastating COVID-19. Botulinum toxins (BoNTs) are potent neurotoxins that can induce paralysis of muscle and acute respiratory arrest in humans. However, a mild dose of the purified form of BoNT has been known to attenuate chronic cough, dyspnoea, pneumonia, acute respiratory failure, abnormal circulation, cardiac defects and various neurological deficits that have been recognised as the prominent clinical symptoms of COVID-19. Considering the fact, this review article provides 1) an overview of the SARS-CoV-2 mediated pathological impact on the lungs, heart and brain, 2) signifies the therapeutic uses of BoNTs against pulmonary failure, cardiac arrest and neurological deficits, and 3) emphasize the rationality for the possible use of BoNT to prevent SARS-CoV-2 infection and manage COVID-19.
Keywords	covid19
Language	English
Publishing date	2020-04-29
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	2590-0986
ISSN (online)	2590-0986
DOI	10.1016/j.medidd.2020.100042
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Perspectives for the use of therapeutic Botulinum toxin as a multifaceted candidate drug to attenuate COVID-19

Mahesh Kandasamy

Medicine in Drug Discovery, Vol 6, Iss , Pp 100042- (2020)

2020

Abstract	The recent outbreak of coronavirus disease (COVID-19) resulting from a distinctive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to evolve in many countries and pose life-threatening clinical issues to global public health. While the lungs are the primary target for the SARS-CoV-2-mediated pathological consequence, the virus appears to invade the brain and cause unpredicted neurological deficits. In the later stage, COVID-19 can progress to pneumonia, acute respiratory failure, neurodegeneration and multi-organ dysfunctions leading to death. Though a significant portion of individuals with COVID-19 has been recovering from clinical symptoms, the pathological impact of the SARS-CoV-2 infection on the structural and functional properties of the lungs, heart, brain and other organs at the post-recovery state remains unknown. Presently, there is an urgent need for a remedial measure to combat this devastating COVID-19. Botulinum toxins (BoNTs) are potent neurotoxins that can induce paralysis of muscle and acute respiratory arrest in humans. However, a mild dose of the purified form of BoNT has been known to attenuate chronic cough, dyspnoea, pneumonia, acute respiratory failure, abnormal circulation, cardiac defects and various neurological deficits that have been recognised as the prominent clinical symptoms of COVID-19. Considering the fact, this review article provides 1) an overview of the SARS-CoV-2 mediated pathological impact on the lungs, heart and brain, 2) signifies the therapeutic uses of BoNTs against pulmonary failure, cardiac arrest and neurological deficits, and 3) emphasize the rationality for the possible use of BoNT to prevent SARS-CoV-2 infection and manage COVID-19.
Keywords	COVID-19 ; Coronavirus ; SARS-CoV-2 ; ACE2 ; Botulinum toxin ; Botox ; Pharmacy and materia medica ; RS1-441 ; covid19
Subject code	610
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Perspectives for the use of therapeutic Botulinum toxin as a multifaceted candidate drug to attenuate COVID-19

Kandasamy, Mahesh

Medicine in Drug Discovery

2020 Volume 6, Page(s) 100042

Keywords	covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ISSN	2590-0986
DOI	10.1016/j.medidd.2020.100042
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Perspectives for the use of therapeutic Botulinum toxin as a multifaceted candidate drug to attenuate COVID-19

Kandasamy, Mahesh

Med Drug Discov

Abstract	The recent outbreak of coronavirus disease (COVID-19) resulting from a distinctive severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to evolve in many countries and pose life-threatening clinical issues to global public health. While the lungs are the primary target for the SARS-CoV-2-mediated pathological consequence, SARS-CoV-2 appear to invade the brain and cause neurological deficits. In the later stage, COVID-19 can progress to pneumonia, acute respiratory failure, neurological deficits and multi-organ dysfunctions leading to death. Though a significant portion of SARS-CoV-2 infected individuals has been recovering from pathological symptoms, the impact of the COVID-19 on the structural and functional properties of the lungs, heart, brain and other organs at the post-recovery state remains unknown. Presently, there is an urgent need for a remedial measure to combat this devastating COVID-19. Botulinum toxins (BoNTs) are potent neurotoxins that can induce paralysis of muscle and acute respiratory arrest in human. However, a mild dose of the purified form of BoNT has been known to attenuate chronic cough, dyspnoea, pneumonia, acute respiratory failure, abnormal circulation, cardiac defects and various neurological deficits that have been recognised as the prominent clinical symptoms of COVID-19. Considering the fact, this review article provides 1) an overview on the SARS-CoV-2 mediated pathological impact on the lungs, heart and brain, 2) signifies the therapeutic uses of BoNTs against pulmonary failure, cardiac arrest and neurological deficits, and 3) emphasize the rationality for the possible use of BoNT to prevent SARS-CoV-2 infection and manage COVID-19.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #141614
Database	COVID19

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Article ; Online: SARS-CoV-2-Mediated Neuropathogenesis, Deterioration of Hippocampal Neurogenesis and Dementia.

Radhakrishnan, Risna K / Kandasamy, Mahesh

American journal of Alzheimer's disease and other dementias

2021 Volume 37, Page(s) 15333175221078418

Abstract: A significant portion of COVID-19 patients and survivors display marked clinical signs of neurocognitive impairments. SARS-CoV-2-mediated peripheral cytokine storm and its neurotropism appear to elicit the activation of glial cells in the brain ... ...

Abstract	A significant portion of COVID-19 patients and survivors display marked clinical signs of neurocognitive impairments. SARS-CoV-2-mediated peripheral cytokine storm and its neurotropism appear to elicit the activation of glial cells in the brain proceeding to neuroinflammation. While adult neurogenesis has been identified as a key cellular basis of cognitive functions, neuroinflammation-induced aberrant neuroregenerative plasticity in the hippocampus has been implicated in progressive memory loss in ageing and brain disorders. Notably, recent histological studies of post-mortem human and experimental animal brains indicate that SARS-CoV-2 infection impairs neurogenic process in the hippocampus of the brain due to neuroinflammation. Considering the facts, this article describes the prominent neuropathogenic characteristics and neurocognitive impairments in COVID-19 and emphasizes a viewpoint that neuroinflammation-mediated deterioration of hippocampal neurogenesis could contribute to the onset and progression of dementia in COVID-19. Thus, it necessitates the unmet need for regenerative medicine for the effective management of neurocognitive deficits in COVID-19.
MeSH term(s)	Animals ; COVID-19 ; Dementia ; Hippocampus ; Humans ; Neurogenesis ; SARS-CoV-2
Language	English
Publishing date	2021-10-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1283069-0
ISSN	1938-2731 ; 0895-5336 ; 1082-5207 ; 1533-3175
ISSN (online)	1938-2731
ISSN	0895-5336 ; 1082-5207 ; 1533-3175
DOI	10.1177/15333175221078418
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Article: Ranitidine Alleviates Anxiety-like Behaviors and Improves the Density of Pyramidal Neurons upon Deactivation of Microglia in the CA3 Region of the Hippocampus in a Cysteamine HCl-Induced Mouse Model of Gastrointestinal Disorder.

Selvaraj, Divya Bharathi / Vergil Andrews, Jemi Feiona / Anusuyadevi, Muthuswamy / Kandasamy, Mahesh

Brain sciences

2023 Volume 13, Issue 2

Abstract: Elevated levels of histamine cause over-secretion of gastric hydrochloric acid (HCl), leading to gastrointestinal (GI) disorders and anxiety. Ranitidine is an antihistamine drug widely used in the management of GI disorders, as it works by blocking the ... ...

Abstract	Elevated levels of histamine cause over-secretion of gastric hydrochloric acid (HCl), leading to gastrointestinal (GI) disorders and anxiety. Ranitidine is an antihistamine drug widely used in the management of GI disorders, as it works by blocking the histamine-2 receptors in parietal cells, thereby reducing the production of HCl in the stomach. While some reports indicate the neuroprotective effects of ranitidine, its role against GI disorder-related anxiety remains unclear. Therefore, we investigated the effect of ranitidine against anxiety-related behaviors in association with changes in neuronal density in the hippocampal cornu ammonis (CA)-3 region of cysteamine hydrochloride-induced mouse model of GI disorder. Results obtained from the open field test (OFT), light and dark box test (LDBT), and elevated plus maze (EPM) test revealed that ranitidine treatment reduces anxiety-like behaviors in experimental animals. Nissl staining and immunohistochemical assessment of ionized calcium-binding adapter molecule (Iba)-1 positive microglia in cryosectioned brains indicated enhanced density of pyramidal neurons and reduced activation of microglia in the hippocampal CA-3 region of brains of ranitidine-treated experimental mice. Therefore, this study suggests that ranitidine mediates anxiolytic effects, which can be translated to establish a pharmacological regime to ameliorate anxiety-related symptoms in humans.
Language	English
Publishing date	2023-02-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2651993-8
ISSN	2076-3425
ISSN	2076-3425
DOI	10.3390/brainsci13020266
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Liposome encapsulated clodronate mediated elimination of pathogenic macrophages and microglia: A promising pharmacological regime to defuse cytokine storm in COVID-19.

Ravichandran, Sowbarnika / Manickam, Nivethitha / Kandasamy, Mahesh

Medicine in drug discovery

2022 Volume 15, Page(s) 100136

Abstract: The emergence of new SARS-CoV-2 variants continues to pose an enormous public health concern. The SARS-CoV-2 infection disrupted host immune response accounting for cytokine storm has been linked to multiorgan failure and mortality in a significant ... ...

Abstract	The emergence of new SARS-CoV-2 variants continues to pose an enormous public health concern. The SARS-CoV-2 infection disrupted host immune response accounting for cytokine storm has been linked to multiorgan failure and mortality in a significant portion of positive cases. Abruptly activated macrophages have been identified as the key pathogenic determinant of cytokine storm in COVID-19. Besides, reactive microglia have been known to discharge a surplus amount of proinflammatory factors leading to neuropathogenic events in the brains of SARS-CoV-2 infected individuals. Considering the fact, depletion of activated macrophages and microglia could be proposed to eradicate the life-threatening cytokine storm in COVID-19. Clodronate, a non-nitrogenous bisphosphonate drug has been identified as a potent macrophage and microglial depleting agent. While recent advancement in the field of liposome encapsulation technology offers the most promising biological tool for drug delivery, liposome encapsulated clodronate has been reported to effectively target and induce prominent phagocytic cell death in activated macrophages and microglia compared to free clodronate molecules. Thus, in this review article, we emphasize that depletion of activated macrophages and microglial cells by administration of liposome encapsulated clodronate can be a potential therapeutic strategy to diminish the pathogenic cytokine storm and alleviate multiorgan failure in COVID-19. Moreover, recently developed COVID-19 vaccines appear to render the chronic activation of macrophages accounting for immunological dysregulation in some cases. Therefore, the use of liposome encapsulated clodronate can also be extended to the clinical management of unforeseen immunogenic reactions resulting from activated macrophages associated adverse effects of COVID-19 vaccines.
Language	English
Publishing date	2022-06-13
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	2590-0986
ISSN (online)	2590-0986
DOI	10.1016/j.medidd.2022.100136
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Article ; Online: Optimization of process parameters to intensify the yield rate of biodiesel derived from waste and inedible Carthamus lanatus (L.) Boiss. seeds and examine the fuel properties with pre-heated water emulsion

Gurusamy, Mahesh / Vellaiyan, Suresh / Kandasamy, Muralidharan / Devarajan, Yuvarajan

Sustainable Chemistry and Pharmacy. 2023 June, v. 33 p.101137-

2023

Abstract: Second-generation biodiesels derived from non-edible feedstocks are a viable alternative to diesel, and the transformation of Asteraceae seeds into biodiesel is the topic of some fascinating research. In the earlier experiments, no attempt was made to ... ...

Abstract	Second-generation biodiesels derived from non-edible feedstocks are a viable alternative to diesel, and the transformation of Asteraceae seeds into biodiesel is the topic of some fascinating research. In the earlier experiments, no attempt was made to optimize Carthamus lanatus (L.) biodiesel (CLB) for a higher yield rate and to discover whether it was suitable for use with a pre-heated water emulsion. The current study aims to extract biodiesel from Carthamus lanatus (L.) Boiss. seeds under optimal conditions, evaluate the effect of reaction parameters on yield rate and determine the appropriateness of pre-heated water-CLB emulsion for fuel applications. The reaction parameters such as catalyst concentration (CC), methanol ratio (MR), impregnation time (ITE) and impregnation temperature (ITP) were optimized using response surface methodology. The function group and chemical constituents of CLB were assessed by Fourier-transform infrared (FTIR) spectroscopy, and Gas chromatography–mass spectrometry (GC-MS). The CLB was blended with various volume concentrations of pre-heated water and their physicochemical properties were assessed. With CC of 2.51737%, MR of 11.0135:1, ITP of 115.625 °C, and ITE of 140.292 min, the CLB yield rate is intensified to 94.51%, and the ITE has a major influence (52%) on yield rate. The FTIR report indicates that the carbon-based components are significantly contributed, and the GC-MS report states that linoleic acid has a maximum contribution. Physicochemical properties reveal that CLB is a suitable alternative to diesel and that up to 15% of the pre-heated water contained in CLB can be used as a direct fuel.
Keywords	Carthamus lanatus ; biodiesel ; catalysts ; emulsions ; feedstocks ; gas chromatography-mass spectrometry ; green chemistry ; linoleic acid ; methanol ; response surface methodology ; temperature ; wastes ; Carthamus lanatus (L.) Boiss. seed oil ; Parametric effects ; Optimization ; Fuel characterization ; Water emulsion
Language	English
Dates of publication	2023-06
Publishing place	Elsevier B.V.
Document type	Article ; Online
ISSN	2352-5541
DOI	10.1016/j.scp.2023.101137
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Pathogenomic Signature and Aberrant Neurogenic Events in Experimental Cerebral Ischemic Stroke: A Neurotranscriptomic-Based Implication for Dementia.

Roshan, Syed Aasish / Elangovan, Gayathri / Gunaseelan, Dharani / Jayachandran, Swaminathan K / Kandasamy, Mahesh / Anusuyadevi, Muthuswamy

Journal of Alzheimer's disease : JAD

2023 Volume 94, Issue s1, Page(s) S289–S308

Abstract: Background: Cerebral ischemic stroke is caused due to neurovascular damage or thrombosis, leading to neuronal dysfunction, neuroinflammation, neurodegeneration, and regenerative failure responsible for neurological deficits and dementia. The valid ... ...

Abstract	Background: Cerebral ischemic stroke is caused due to neurovascular damage or thrombosis, leading to neuronal dysfunction, neuroinflammation, neurodegeneration, and regenerative failure responsible for neurological deficits and dementia. The valid therapeutic targets against cerebral stroke remain obscure. Thus, insight into neuropathomechanisms resulting from the aberrant expression of genes appears to be crucial. Objective: In this study, we have elucidated how neurogenesis-related genes are altered in experimental stroke brains from the available transcriptome profiles in correlation with transcriptome profiles of human postmortem stroke brain tissues. Methods: The transcriptome datasets available on the middle cerebral artery occlusion (MCAo) rat brains were obtained from the Gene Expression Omnibus, National Center for Biotechnology Information. Of the available datasets, 97 samples were subjected to the meta-analysis using the network analyst tool followed by Cytoscape-based enrichment mapping analysis. The key differentially expressed genes (DEGs) were validated and compared with transcriptome profiling of human stroke brains. Results: Results revealed 939 genes are differently expressed in the brains of the MCAo rat model of stroke, in which 30 genes are key markers of neural stem cells, and regulators of neurogenic processes. Its convergence with DEGs from human stroke brains has revealed common targets. Conclusion: This study has established a panel of highly important DEGs to signify the potential therapeutic targets for neuroregenerative strategy against pathogenic events associated with cerebral stroke. The outcome of the findings can be translated to mitigate neuroregeneration failure seen in various neurological and metabolic disease manifestations with neurocognitive impairments.
MeSH term(s)	Rats ; Humans ; Animals ; Ischemic Stroke/complications ; Stroke/genetics ; Stroke/complications ; Brain/pathology ; Infarction, Middle Cerebral Artery/complications ; Infarction, Middle Cerebral Artery/genetics ; Neurogenesis ; Dementia/complications
Language	English
Publishing date	2023-02-13
Publishing country	Netherlands
Document type	Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-220831
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