Neuroprotective potential of Celastrus paniculatus seeds against common neurological ailments: a narrative review

2022 ◽  
Vol 0 (0) ◽  
Author(s):  
Divya Sankaramourthy ◽  
Lakshmi Sankaranarayanan ◽  
Kavimani Subramanian ◽  
Sudha Rani Sadras
Keyword(s):  
Neurological Disorders ◽  
Seed Oil ◽  
Oxygen Free Radicals ◽  
Therapeutic Potential ◽  
Neuronal Damage ◽  
Treatment Strategies ◽  
Unfolded Proteins ◽  
Complex Interplay ◽  
Drug Candidates ◽  
Celastrus Paniculatus

Abstract The most common human neurodegenerative diseases like Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) etc. have been recognized to result from a complex interplay between genetic predisposition and defective cellular dynamics such as inappropriate accumulation of unfolded proteins, oxygen free radicals and mitochondrial dysfunction. The treatment strategies available today for these neurodegenerative ailments are only palliative and are incapable of restraining the progression of the disease. Hence, there is an immense requirement for identification of drug candidates with the ability to alleviate neuronal damage along with controlling progression of the disease. From time immemorial mankind has been relying on plants for treating varied types of dreadful diseases. Among the various medicinal plants used for treating various neurological ailments, Celastrus paniculatus (CP) popularly known as Jyotishmati or Malkangni is well known in the Ayurveda system of Indian Traditional Medicine whose seeds and seed oil have been used for centuries in treating epilepsy, dementia, facial paralysis, amnesia, anxiety, sciatica, cognitive dysfunctions etc. This review apart from specifying the phytochemical characteristics and traditional uses of C. paniculatus seeds and seed oil also exemplify the comprehensive data derived from various research reports on their therapeutic potential against some common neurological disorders.

scholarly journals Clinical Relevance of Cortical Spreading Depression in Neurological Disorders: Migraine, Malignant Stroke, Subarachnoid and Intracranial Hemorrhage, and Traumatic Brain Injury

2010 ◽  
Vol 31 (1) ◽  
pp. 17-35 ◽  
Author(s):  
Martin Lauritzen ◽  
Jens Peter Dreier ◽  
Martin Fabricius ◽  
Jed A Hartings ◽  
Rudolf Graf ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurological Disorders ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Neuronal Damage ◽  
Ion Homeostasis ◽  
Large Body ◽  
Treatment Strategies ◽  
Pathophysiological Mechanism

Cortical spreading depression (CSD) and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow (CBF). There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine, stroke, subarachnoid hemorrhage and traumatic brain injury. The implications of these findings are widespread and suggest that intrinsic brain mechanisms have the potential to worsen the outcome of cerebrovascular episodes or brain trauma. The consequences of these intrinsic mechanisms are intimately linked to the composition of the brain extracellular microenvironment and to the level of brain perfusion and in consequence brain energy supply. This paper summarizes the evidence provided by novel invasive techniques, which implicates CSD as a pathophysiological mechanism for this group of acute neurological disorders. The findings have implications for monitoring and treatment of patients with acute brain disorders in the intensive care unit. Drawing on the large body of experimental findings from animal studies of CSD obtained during decades we suggest treatment strategies, which may be used to prevent or attenuate secondary neuronal damage in acutely injured human brain cortex caused by depolarization waves.

In-silico prediction of the beta carboline alkaloids Harmine and Harmaline as potent drug candidates for the treatment of Parkinson’s disease

2020 ◽  
Vol 19 ◽  
Author(s):  
Rumpa Banerjee ◽  
Mukesh Kumar ◽  
Isha Gaurav ◽  
Sudha Thakur ◽  
Abhimanyu Thakur ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Docking ◽  
Dopamine Receptors ◽  
Binding Affinity ◽  
In Silico ◽  
Therapeutic Potential ◽  
Treatment Strategies ◽  
Toxicity Profile ◽  
Drug Candidates

Background:: Parkinson’s disease (PD) is a progressive neurodegenerative disease manifested by core symptoms of loss of motor control and postural instability. Loss of dopaminergic neurons is the cause of PD, thus enhancing dopamine level by pharmacological treatment is one of the key treatment strategies for PD. However, limitations of current treatment strategies open the possibility of novel drug candidates for the treatment of PD. Objective:: To investigate the anti-PD potential of Harmine and Harmaline. We aim to evaluate the therapeutic potential of Harmine and Harmaline by in-silico approaches; molecular docking, pharmacokinetic and Prediction of Activity Spectra for Substances (PASS) analysis were used for evaluating the therapeutic potential of Harmine and Harmaline and standard drug levodopa (L-DOPA). Methods:: Auto dock vina was used for molecular docking of all three compounds against D2- and D3- dopamine receptors. The pharmacokinetics (PKs) and toxicity profile were predicted by pkCSM and the pharmacological activity was predicted by PASS analysis. Results:: Molecular docking showed a higher binding affinity of Harmine and Harmaline as compared to L-DOPA, and these results were supported by in-silico pharmacokinetic and toxicity profiling. Moreover, PASS analysis showed anti-PD activi-ty of Harmine and Harmaline. Conclusion:: Harmine and Harmaline exhibit higher binding affinity towards D2- and D3- dopamine receptors compared to L-DOPA, and PKs and toxicity profile support their potential as drug candidates for PD therapy.

Therapeutic Potential of Phosphodiesterase Inhibitors for Endothelial Dysfunction- Related Diseases

2020 ◽  
Vol 26 (30) ◽  
pp. 3633-3651 ◽  
Author(s):  
Javier Blanco-Rivero ◽  
Fabiano E. Xavier
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Therapeutic Potential ◽  
Treatment Strategies ◽  
Phosphodiesterase Inhibitors ◽  
Developed Countries ◽  
Major Health Problem ◽  
Pde Inhibitors ◽  
Pharmaceutical Industries

Cardiovascular diseases (CVD) are considered a major health problem worldwide, being the main cause of mortality in developing and developed countries. Endothelial dysfunction, characterized by a decline in nitric oxide production and/or bioavailability, increased oxidative stress, decreased prostacyclin levels, and a reduction of endothelium-derived hyperpolarizing factor is considered an important prognostic indicator of various CVD. Changes in cyclic nucleotides production and/ or signalling, such as guanosine 3', 5'-monophosphate (cGMP) and adenosine 3', 5'-monophosphate (cAMP), also accompany many vascular disorders that course with altered endothelial function. Phosphodiesterases (PDE) are metallophosphohydrolases that catalyse cAMP and cGMP hydrolysis, thereby terminating the cyclic nucleotide-dependent signalling. The development of drugs that selectively block the activity of specific PDE families remains of great interest to the research, clinical and pharmaceutical industries. In the present review, we will discuss the effects of PDE inhibitors on CVD related to altered endothelial function, such as atherosclerosis, diabetes mellitus, arterial hypertension, stroke, aging and cirrhosis. Multiple evidences suggest that PDEs inhibition represents an attractive medical approach for the treatment of endothelial dysfunction-related diseases. Selective PDE inhibitors, especially PDE3 and PDE5 inhibitors are proposed to increase vascular NO levels by increasing antioxidant status or endothelial nitric oxide synthase expression and activation and to improve the morphological architecture of the endothelial surface. Thereby, selective PDE inhibitors can improve the endothelial function in various CVD, increasing the evidence that these drugs are potential treatment strategies for vascular dysfunction and reinforcing their potential role as an adjuvant in the pharmacotherapy of CVD.

scholarly journals mRNA-Driven Generation of Transgene-Free Neural Stem Cells from Human Urine-Derived Cells

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1043 ◽  
Author(s):  
Phil Jun Kang ◽  
Daryeon Son ◽  
Tae Hee Ko ◽  
Wonjun Hong ◽  
Wonjin Yun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Human Urine ◽  
Neurological Disorders ◽  
Therapeutic Potential ◽  
Embryonic Stem ◽  
Global Gene Expression ◽  
Patient Specific ◽  
Human Neural Stem Cells

Human neural stem cells (NSCs) hold enormous promise for neurological disorders, typically requiring their expandable and differentiable properties for regeneration of damaged neural tissues. Despite the therapeutic potential of induced NSCs (iNSCs), a major challenge for clinical feasibility is the presence of integrated transgenes in the host genome, contributing to the risk for undesired genotoxicity and tumorigenesis. Here, we describe the advanced transgene-free generation of iNSCs from human urine-derived cells (HUCs) by combining a cocktail of defined small molecules with self-replicable mRNA delivery. The established iNSCs were completely transgene-free in their cytosol and genome and further resembled human embryonic stem cell-derived NSCs in the morphology, biological characteristics, global gene expression, and potential to differentiate into functional neurons, astrocytes, and oligodendrocytes. Moreover, iNSC colonies were observed within eight days under optimized conditions, and no teratomas formed in vivo, implying the absence of pluripotent cells. This study proposes an approach to generate transplantable iNSCs that can be broadly applied for neurological disorders in a safe, efficient, and patient-specific manner.

scholarly journals Unravelling the Complex Interplay of Transcription Factors Orchestrating Seed Oil Content in Brassica napus L.

2021 ◽  
Vol 22 (3) ◽  
pp. 1033
Author(s):  
Abirami Rajavel ◽  
Selina Klees ◽  
Johanna-Sophie Schlüter ◽  
Hendrik Bertram ◽  
Kun Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Brassica Napus ◽  
Oil Content ◽  
Seed Oil ◽  
Seed Oil Content ◽  
Complex Interplay ◽  
Brassica Napus L ◽  
Data Set ◽  
Developmental Switches

Transcription factors (TFs) and their complex interplay are essential for directing specific genetic programs, such as responses to environmental stresses, tissue development, or cell differentiation by regulating gene expression. Knowledge regarding TF–TF cooperations could be promising in gaining insight into the developmental switches between the cultivars of Brassica napus L., namely Zhongshuang11 (ZS11), a double-low accession with high-oil- content, and Zhongyou821 (ZY821), a double-high accession with low-oil-content. In this regard, we analysed a time series RNA-seq data set of seed tissue from both of the cultivars by mainly focusing on the monotonically expressed genes (MEGs). The consideration of the MEGs enables the capturing of multi-stage progression processes that are orchestrated by the cooperative TFs and, thus, facilitates the understanding of the molecular mechanisms determining seed oil content. Our findings show that TF families, such as NAC, MYB, DOF, GATA, and HD-ZIP are highly involved in the seed developmental process. Particularly, their preferential partner choices as well as changes in their gene expression profiles seem to be strongly associated with the differentiation of the oil content between the two cultivars. These findings are essential in enhancing our understanding of the genetic programs in both cultivars and developing novel hypotheses for further experimental studies.

scholarly journals The Potential Association between the Risk of Post-Surgical Adhesion and the Activated Local Angiotensin II Type 1 Receptors: Need for Novel Treatment Strategies

2021 ◽  
pp. 1-8
Author(s):  
Mahmood Tavakkoli ◽  
Saeed Aali ◽  
Borzoo Khaledifar ◽  
Gordon A. Ferns ◽  
Majid Khazaei ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Therapeutic Potential ◽  
Angiotensin Receptor Blockers ◽  
Surgical Techniques ◽  
Treatment Strategies ◽  
Transforming Growth Factor Β

<b><i>Background:</i></b> Post-surgical adhesion bands (PSABs) are a common complication after abdominal or pelvic surgeries for different reasons like cancer treatment. Despite improvements in surgical techniques and the administration of drugs or the use of physical barriers, there has only been limited improvement in the frequency of postoperative adhesions. Complications of PSAB are pain, infertility, intestinal obstruction, and increased mortality. The most important molecular mechanisms for the development of PSAB are inflammatory response, oxidative stress, and overexpression of pro-fibrotic molecules such as transforming growth factor β. However, questions remain about the pathogenesis of this problem, for example, the causes for individual differences or why certain tissue sites are more prone to post-surgical adhesions. <b><i>Summary:</i></b> Addressing the pathological causes of PSAB, the potential role of local angiotensin II/angiotensin II type 1 receptors (AngII/AT1R), may help to prevent this problem. <b><i>Key Message:</i></b> The objective of this article was to explore the role of the AngII/AT1R axis potential to induce PSAB and the therapeutic potential of angiotensin receptor blockers in the prevention and treatment of PSAB.

Assessment of the therapeutic potential of hesperidin and proteomic resolution of diabetes-mediated neuronal fluctuations expediting Alzheimer’s disease

RSC Advances ◽  
2015 ◽  
Vol 5 (58) ◽  
pp. 46965-46980 ◽  
Author(s):  
Sapna Khowal ◽  
Malik M. A. Mustufa ◽  
Naveen K. Chaudhary ◽  
Samar Husain Naqvi ◽  
Suhel Parvez ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Therapeutic Potential ◽  
Neuronal Damage ◽  
Early Stage ◽  
Type Iii

Alzheimer’s disease (AD) has been proposed as type III diabetes mellitus. Prognosis and early stage diagnosis of AD is essentially required in diabetes to avoid extensive irreversible neuronal damage.

Natural products targeting cancer stem cells: a revisit

2021 ◽  
Vol 28 ◽  
Author(s):  
Jiahua Cui ◽  
Jiajun Qian ◽  
Larry Ming-Cheung Chow ◽  
Jinping Jia
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Natural Products ◽  
Cancer Stem Cells ◽  
Therapeutic Potential ◽  
Tumor Development ◽  
Biologically Active ◽  
Cellular Targets ◽  
Drug Candidates ◽  
Enhanced Expression

Background: The proposed central role of cancer stem cells (CSCs) in tumor development has been extended to explain the diverse oncologic phenomena such as multidrug resistance, metastasis and tumor recurrence in clinics. Due to the enhanced expression of ATP-binding cassette transporters and anti-apoptotic factors, stagnation on G0 phase and the strong ability of self-renewal, the CSCs were highly resistant to clinical anticancer drugs. Therefore, the discovery of new drug candidates that could effectively eradicate cancer stem cells afforded promising outcomes in cancer therapy. Introduction: Natural products and their synthetic analogues are a rich source of biologically active compounds and several of them have already been recognized as potent CSCs killers. We aim to provide a collection of recently identified natural products that suppressed the survival of the small invasive CSC populations and combated the drug resistance of these cells in chemotherapy. Results and Conclusion: These anti-CSCs natural products included flavonoids, stilbenes, quinones, terpenoids, polyketide antibiotics, steroids and alkaloids. In the present review, we highlighted the therapeutic potential of natural products and their derivatives against the proliferation and drug resistance of CSCs, their working mechanisms and related structure-activity relationships. Meanwhile, in this survey, several natural products with diverse cellular targets such as the naphthoquinone shikonin and the stilbene resveratrol were characterized as promising lead compounds for future development.

Therapeutic potential of biogenic titanium dioxide nanoparticles: a review on mechanistic approaches

Nanomedicine ◽  
2021 ◽  
Author(s):  
Muhammad Ikram ◽  
Bilal Javed ◽  
Syed Wajeeh Ul Hassan ◽  
Seema Hassan Satti ◽  
Abdullah Sarwer ◽  
...  
Keyword(s):  
Titanium Dioxide ◽  
Molecular Level ◽  
Therapeutic Potential ◽  
Titanium Dioxide Nanoparticles ◽  
Treatment Strategies ◽  
Future Application ◽  
Physiological Mechanisms ◽  
Biogenic Synthesis ◽  
Disease Prognosis ◽  
Transport Chain

Biogenic titanium dioxide nanoparticles have unique size, shape and biochemical functional corona that embellish them with the potential to perform therapeutic actions such as anticancer, antimicrobial, antioxidant, larvicidal and photocatalysis by adopting various mechanistic or physiological approaches at the molecular level. We have provided a detailed overview of some of these physiological mechanisms, including disruption of the electron transport chain, DNA fragmentation, mitochondrial damage, induction of apoptosis, disorganization of the plasma membrane, inhibition of ATP synthase activity, suspension of cellular signaling pathways and inhibition of enzymatic activity. The biogenic synthesis of customized titanium dioxide nanoparticles has future application potentials to do breakthroughs in the pharmaceutical sectors to advance precision medicine and to better explain the disease prognosis and treatment strategies.

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