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Article ; Online: Exploring sulforaphane as neurotherapeutic: targeting Nrf2-Keap & Nf-Kb pathway crosstalk in ASD.

Shah, Ali / Varma, Manasi / Bhandari, Ranjana

2023 Volume 39, Issue 3, Page(s) 373–385

Abstract: Autism spectrum disorders (ASD) are a family of complex neurodevelopmental disorders, characterized mainly through deficits in social behavior and communication. While the causes giving rise to autistic symptoms are numerous and varied, the treatment ... ...

Abstract	Autism spectrum disorders (ASD) are a family of complex neurodevelopmental disorders, characterized mainly through deficits in social behavior and communication. While the causes giving rise to autistic symptoms are numerous and varied, the treatment options and therapeutic avenues are still severely limited. Nevertheless, a number of signalling pathways have been implicated in the pathogenesis of the disease, and targeting these pathways might provide insight into potential treatments and future strategies. Importantly, alterations in inflammation, oxidative stress, and mitochondrial dysfunction have been noted in the brains of ASD patients, and among the pathways involved in these processes is the Nrf2 cascade. This particular pathway has been hypothesized to be involved in inducing both, inflammatory and anti-inflammatory/neuroprotective effects in the brain, sparking an interest in its use in ASD. Sulforaphane, a sulfur-containing phytochemical present mainly in cruciferous plants like broccoli and cabbage, has shown efficacy in activating the Nrf2 signaling pathway, which in turn brings about a protective effect on neuronal cells, especially against mitochondrial dysfunction. Its efficacy against ASD has not yet been evaluated, and in this paper, we attempt to discuss the therapeutic potential of this agent in the therapy of autism, with special emphasis on the role of the Nrf2 pathway in the disorder.
MeSH term(s)	Humans ; NF-kappa B ; NF-E2-Related Factor 2/metabolism ; Autism Spectrum Disorder/drug therapy ; Autism Spectrum Disorder/metabolism ; Mitochondrial Diseases ; Sulfoxides ; Isothiocyanates
Chemical Substances	NF-kappa B ; NF-E2-Related Factor 2 ; sulforaphane (GA49J4310U) ; Sulfoxides ; Isothiocyanates
Language	English
Publishing date	2023-05-30
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	632824-6
ISSN	1573-7365 ; 0885-7490
ISSN (online)	1573-7365
ISSN	0885-7490
DOI	10.1007/s11011-023-01224-4
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Article ; Online: Repurposing Niclosamide as a plausible neurotherapeutic in autism spectrum disorders, targeting mitochondrial dysfunction: a strong hypothesis.

Varma, Manasi / Bhandari, Ranjana / Kuhad, Anurag

Metabolic brain disease

2023 Volume 39, Issue 3, Page(s) 387–401

Abstract: Autism Spectrum Disorders (ASD) are a complex set of neurodevelopmental manifestations which present in the form of social and communication deficits. Affecting a growing proportion of children worldwide, the exact pathogenesis of this disorder is not ... ...

Abstract	Autism Spectrum Disorders (ASD) are a complex set of neurodevelopmental manifestations which present in the form of social and communication deficits. Affecting a growing proportion of children worldwide, the exact pathogenesis of this disorder is not very well understood, and multiple signaling pathways have been implicated. Among them, the ERK/MAPK pathway is critical in a number of cellular processes, and the normal functioning of neuronal cells also depends on this cascade. As such, recent studies have increasingly focused on the impact this pathway has on the development of autistic symptoms. Improper ERK signaling is suspected to be involved in neurotoxicity, and the same might be implicated in autism spectrum disorders (ASD), through a variety of effects including mitochondrial dysfunction and oxidative stress. Niclosamide, an antihelminthic and anti-inflammatory agent, has shown potential in inhibiting this pathway, and countering the effects shown by its overactivity in inflammation. While it has previously been evaluated in other neurological disorders like Alzheimer's Disease and Parkinson's Disease, as well as various cancers by targeting ERK/MAPK, it's efficacy in autism has not yet been evaluated. In this article, we attempt to discuss the potential role of the ERK/MAPK pathway in the pathogenesis of ASD, specifically through mitochondrial damage, before moving to the therapeutic potential of niclosamide in the disorder, mediated by the inhibition of this pathway and its detrimental effects of neuronal development.
MeSH term(s)	Child ; Humans ; Autism Spectrum Disorder/drug therapy ; Autism Spectrum Disorder/metabolism ; Niclosamide/pharmacology ; Niclosamide/therapeutic use ; Autistic Disorder ; Oxidative Stress ; Mitochondrial Diseases
Chemical Substances	Niclosamide (8KK8CQ2K8G)
Language	English
Publishing date	2023-06-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	632824-6
ISSN	1573-7365 ; 0885-7490
ISSN (online)	1573-7365
ISSN	0885-7490
DOI	10.1007/s11011-023-01247-x
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Article ; Online: Taurine as a potential therapeutic agent interacting with multiple signaling pathways implicated in autism spectrum disorder (ASD): An in-silico analysis.

Bhandari, Ranjana / Varma, Manasi / Rana, Priyanka / Dhingra, Neelima / Kuhad, Anurag

IBRO neuroscience reports

2023 Volume 15, Page(s) 170–177

Abstract: Autism spectrum disorders (ASD) are a complex sequelae of neurodevelopmental disorders which manifest in the form of communication and social deficits. Currently, only two agents, namely risperidone and aripiprazole have been approved for the treatment ... ...

Abstract	Autism spectrum disorders (ASD) are a complex sequelae of neurodevelopmental disorders which manifest in the form of communication and social deficits. Currently, only two agents, namely risperidone and aripiprazole have been approved for the treatment of ASD, and there is a dearth of more drugs for the disorder. The exact pathophysiology of autism is not understood clearly, but research has implicated multiple pathways at different points in the neuronal circuitry, suggesting their role in ASD. Among these, the role played by neuroinflammatory cascades like the NF-KB and Nrf2 pathways, and the excitotoxic glutamatergic system, are said to have a bearing on the development of ASD. Similarly, the GPR40 receptor, present in both the gut and the blood brain barrier, has also been said to be involved in the disorder. Consequently, molecules which can act by interacting with one or multiple of these targets might have a potential in the therapy of the disorder, and for this reason, this study was designed to assess the binding affinity of taurine, a naturally-occurring amino acid, with these target molecules. The same was scored against these targets using
Language	English
Publishing date	2023-09-02
Publishing country	Netherlands
Document type	Journal Article
ISSN	2667-2421
ISSN (online)	2667-2421
DOI	10.1016/j.ibneur.2023.08.2191
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Article ; Online: Major depressive disorder (mdd): emerging immune targets at preclinical level.

Varma, Manasi / Kaur, Arshpreet / Bhandari, Ranjana / Kumar, Ashwani / Kuhad, Anurag

Expert opinion on therapeutic targets

2023 Volume 27, Issue 6, Page(s) 479–501

Abstract: Background: Major depressive disorder is a mental health disorder that is characterized by a persistently low mood and loss of interest. MDD is affecting over 3.8% of the global population as a major health problem. Its etiology is complex, and involves ...

Abstract	Background: Major depressive disorder is a mental health disorder that is characterized by a persistently low mood and loss of interest. MDD is affecting over 3.8% of the global population as a major health problem. Its etiology is complex, and involves the interaction between a number of factors, including genetic predisposition and the presence of environmental stresses. Areas covered: The role of the immune and inflammatory systems in depression has been gaining interest, with evidence suggesting the potential involvement of pro-inflammatory molecules like TNF, interleukins, prostaglandins, and other cytokines, among others, has been put forth. Along with this, the potential of agents, from NSAIDs to antibiotics, are being evaluated in therapy for depression. The current review will discuss emerging immune targets at the preclinical level. Expert opinion: With increasing evidence to show that immune and inflammatory mediators are implicated in MDD, increasing research toward their potential as drug targets is encouraged. At the same time, agents acting on these mediators and possessing anti-inflammatory potential are also being evaluated as future therapeutic options for MDD, and increasing focus toward non-conventional drugs which can act through these mechanisms is important as regards the future prospects of the use of anti-inflammatory agents in depression.
MeSH term(s)	Humans ; Depressive Disorder, Major/drug therapy ; Cytokines ; Anti-Inflammatory Agents ; Inflammation Mediators ; Anti-Bacterial Agents
Chemical Substances	Cytokines ; Anti-Inflammatory Agents ; Inflammation Mediators ; Anti-Bacterial Agents
Language	English
Publishing date	2023-06-26
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2055208-7
ISSN	1744-7631 ; 1472-8222
ISSN (online)	1744-7631
ISSN	1472-8222
DOI	10.1080/14728222.2023.2225216
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Article: Novel Nanotechnological Approaches for Targeting Dorsal Root Ganglion (DRG) in Mitigating Diabetic Neuropathic Pain (DNP).

Bhandari, Ranjana / Sharma, Ashmita / Kuhad, Anurag

Frontiers in endocrinology

2022 Volume 12, Page(s) 790747

Abstract: Diabetic neuropathy is the most entrenched complication of diabetes. Usually, it affects the distal foot and toes, which then gradually approaches the lower part of the legs. Diabetic foot ulcer (DFU) could be one of the worst complications of diabetes ... ...

Abstract	Diabetic neuropathy is the most entrenched complication of diabetes. Usually, it affects the distal foot and toes, which then gradually approaches the lower part of the legs. Diabetic foot ulcer (DFU) could be one of the worst complications of diabetes mellitus. Long-term diabetes leads to hyperglycemia, which is the utmost contributor to neuropathic pain. Hyperglycemia causing an upregulation of voltage-gated sodium channels in the dorsal root ganglion (DRG) was often observed in models of neuropathic pain. DRG opening frequency increases intracellular sodium ion levels, which further causes increased calcium channel opening and stimulates other pathways leading to diabetic peripheral neuropathy (DPN). Currently, pain due to diabetic neuropathy is managed
MeSH term(s)	Animals ; Diabetes Mellitus, Experimental/metabolism ; Diabetic Neuropathies/drug therapy ; Ganglia, Spinal/metabolism ; Humans ; Liposomes ; Nanoparticles ; Nanotechnology ; Neuralgia/drug therapy ; Neuralgia/etiology
Chemical Substances	Lipid Nanoparticles ; Liposomes
Language	English
Publishing date	2022-02-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2021.790747
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Article: Novel nanotechnological approaches for treatment of skin-aging.

Sharma, Ashmita / Kuhad, Anurag / Bhandari, Ranjana

Journal of tissue viability

2022 Volume 31, Issue 3, Page(s) 374–386

Abstract: One of the essential organs and protective barricades, the skin, needs to be taken care of early. Skin is affected by several intrinsic and extrinsic factors, and despite their morphological and pathological differences, they have many molecular ... ...

Abstract	One of the essential organs and protective barricades, the skin, needs to be taken care of early. Skin is affected by several intrinsic and extrinsic factors, and despite their morphological and pathological differences, they have many molecular similarities. As of today, various mechanisms and theories have been recommended for aging, such as cellular anility, reduced proliferative tendency, reduction in length of telomere, mutations in DNA, theory of free radical generation, and many others. In today's society, skin health is often considered an important indicator of health, which has led to an increased demand for anti-aging products. However, numerous conventional cosmetics and phytocompounds (curcumin, Vitamin E, resveratrol) utilized in anti-aging products have inimical physical and chemical attributes, including insufficient chemical stability and inadequate skin penetration bound their effectuality after topical administration. So recently, new novel nanotechnological approaches for preventing skin aging, such as liposomes, niosomes, solid lipid nanoparticles, transferosomes, ethosomes, nanostructured lipid carriers, and carbon nanotubes, are being used. Hence, the field of cosmeceutical nanomaterials is rapidly evolving, and we can look forward to seeing a variety of innovative nanotechnology-based cosmetic products be a game-changer for this multi-million anti-aging cosmetic industry.
MeSH term(s)	Cosmetics/pharmacology ; Cosmetics/therapeutic use ; Humans ; Liposomes ; Nanoparticles ; Nanotechnology ; Nanotubes, Carbon ; Skin/metabolism ; Skin Aging
Chemical Substances	Cosmetics ; Lipid Nanoparticles ; Liposomes ; Nanotubes, Carbon
Language	English
Publishing date	2022-05-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1282604-2
ISSN	0965-206X
ISSN	0965-206X
DOI	10.1016/j.jtv.2022.04.010
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Article ; Online: Nitric oxide pathway as a plausible therapeutic target in autism spectrum disorders.

Mehta, Rishab / Kuhad, Anurag / Bhandari, Ranjana

Expert opinion on therapeutic targets

2022 Volume 26, Issue 7, Page(s) 659–679

Abstract: Background: The nitric oxide pathway has been \pivotal in exploring neurodevelopmental disorders. Pathogenesis of autism spectrum disorders (ASD) is also suspected to involve a number of biological cascades triggered by nitric oxide-induced ... ...

Abstract	Background: The nitric oxide pathway has been \pivotal in exploring neurodevelopmental disorders. Pathogenesis of autism spectrum disorders (ASD) is also suspected to involve a number of biological cascades triggered by nitric oxide-induced neurotoxicity. The excessive nitric oxide levels caused by varied toxicants leads to the formation of reactive nitrogenous species along with ROS leading to mitochondrial dysfunction, oxidative stress, neuroinflammation, and altered NOS expression responsible for worsening of behavioral complications. Areas covered: In this article, we will discuss the plausible role of the nitric oxide pathway in ASD and also discuss the modulation of this pathway by therapeutics, which can be explored in clinics for mitigating nitrosative stress in ASD. Literature was searched utilizing various databases such as Embase, Medline, Web of Science, and Google Scholar from 1966 to 2021. Expert opinion: Nitric oxide pathway is an unexplored domain in the field of ASD and could act as an important therapeutic target in providing relief from behavioral alterations in autistic patients. At present, no major experimental study confirms the role of nitric oxide in autism. However, conclusive preclinical and clinical evidence is needed to evaluate and establish the role of nitric oxide in ASD.
MeSH term(s)	Autism Spectrum Disorder/drug therapy ; Humans ; Nitric Oxide/metabolism ; Nitrosative Stress ; Oxidative Stress
Chemical Substances	Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2022-07-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2055208-7
ISSN	1744-7631 ; 1472-8222
ISSN (online)	1744-7631
ISSN	1472-8222
DOI	10.1080/14728222.2022.2100252
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Article ; Online: Enhanced Bioavailability and Higher Uptake of Brain-Targeted Surface Engineered Delivery System of Naringenin developed as a Therapeutic for Autism Spectrum Disorder.

Bhandari, Ranjana / Paliwal, Jyoti K / Kuhad, Anurag

Current drug delivery

2022 Volume 20, Issue 2, Page(s) 158–182

Abstract: Background: Neuroinflammation resulting from oxidative and nitrosative stress is associated with various neurological disorders and involves the generation of pro-inflammatory cytokines and microglial activation. Dietary phytochemicals are safer and ... ...

Abstract	Background: Neuroinflammation resulting from oxidative and nitrosative stress is associated with various neurological disorders and involves the generation of pro-inflammatory cytokines and microglial activation. Dietary phytochemicals are safer and more valuable adjunct neurotherapeutic agents which can be added to the therapeutic regimen. These compounds provide neuroprotection by the modulation of various signaling pathways. Introduction: Naringenin (NGN) is a phytochemical having low oral bioavailability because of poor solubility, and adding to this limitation is enhanced efflux by P-glycoprotein transporters in neuroinflammatory diseases. Methods: Hence, as a solution for these limitations, naringenin encapsulated poly-lactic-co-glycolic acid (PLGA) nanocarriers were developed using the nanoprecipitation technique and coated with 1% glutathione (GSH) and 1% Tween 80 to enhance brain delivery. Results: Coated and uncoated NGN-PLGA nanoparticles (NGN-PLGA-NPs) were spherical, monodispersed, stable, and non-toxic, with a particle size of less than 200 nm. They had negative zeta-potential values, 80% entrapment efficiency, and sustained drug release of 81.8% (uncoated), 80.13%, and 78.43% (coated) in 24 hours. FT-IR, DSC, PXRD, and NMR confirmed the drug encapsulation and coating over nanoparticles. In vivo brain uptake showed greater fluorescence intensity of the coated nanoparticles in the brain than uncoated nanoparticles. In addition, there was a 2.33-fold increase in bioavailability after coating compared to naringenin suspension and enhanced brain uptake. Conclusion: Present studies indicate sustained and targeted brain delivery of naringenin via the ligandcoated delivery system by inhibiting enhanced P-glycoprotein (P-gp) efflux occurring in autism spectrum disorders due to neuroinflammation.
MeSH term(s)	Humans ; Biological Availability ; Autism Spectrum Disorder ; Neuroinflammatory Diseases ; Spectroscopy, Fourier Transform Infrared ; Brain ; ATP Binding Cassette Transporter, Subfamily B ; Glycols ; Nanoparticles ; Particle Size ; Drug Carriers
Chemical Substances	naringenin (HN5425SBF2) ; ATP Binding Cassette Transporter, Subfamily B ; Glycols ; Drug Carriers
Language	English
Publishing date	2022-03-03
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	2185284-4
ISSN	1875-5704 ; 1567-2018
ISSN (online)	1875-5704
ISSN	1567-2018
DOI	10.2174/1567201819666220303101506
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Article ; Online: Correspondence regarding: TLR4 as a therapeutic target for respiratory and neurological complications of SARS-CoV-2.

Kaushik, Dhriti / Bhandari, Ranjana / Kuhad, Anurag

Expert opinion on therapeutic targets

2021 Volume 25, Issue 10, Page(s) 911

MeSH term(s)	COVID-19 ; Cytokine Release Syndrome ; Humans ; Nervous System Diseases ; SARS-CoV-2 ; Toll-Like Receptor 4
Chemical Substances	TLR4 protein, human ; Toll-Like Receptor 4
Language	English
Publishing date	2021-11-28
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2055208-7
ISSN	1744-7631 ; 1472-8222
ISSN (online)	1744-7631
ISSN	1472-8222
DOI	10.1080/14728222.2021.2005578
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Article ; Online: TLR4 as a therapeutic target for respiratory and neurological complications of SARS-CoV-2.

Kaushik, Dhriti / Bhandari, Ranjana / Kuhad, Anurag

Expert opinion on therapeutic targets

2021 Volume 25, Issue 6, Page(s) 491–508

Abstract: ... ...

Abstract	Introduction
MeSH term(s)	Animals ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19/complications ; Humans ; Lung Diseases/complications ; Nervous System Diseases/complications ; Retrospective Studies ; SARS-CoV-2/isolation & purification ; Toll-Like Receptor 4/drug effects ; COVID-19 Drug Treatment
Chemical Substances	Antiviral Agents ; Toll-Like Receptor 4
Language	English
Publishing date	2021-04-28
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2055208-7
ISSN	1744-7631 ; 1472-8222
ISSN (online)	1744-7631
ISSN	1472-8222
DOI	10.1080/14728222.2021.1918103
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