Publications by authors named "Devesh Tewari"

49 Publications

Epidemiologic profile and outcome of primary pediatric brain tumors in Iran: retrospective study and literature review.

Childs Nerv Syst 2021 Sep 24. Epub 2021 Sep 24.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144411, India.

Purpose: Primary pediatric tumors are the most common solid tumors in children. There are limited reports on the management and outcome of these tumors in the developing countries. In recent years, advances have been done in the diagnosis, treatment, and outcome of these tumors. The aim of this study was to evaluate the histopathology, characteristics, and outcome of primary pediatric tumors in Iran.

Methods: This retrospective study examines primary brain tumors in children below 14 years of age who have undergone surgery. Histopathological characteristics according to WHO 2017 classification, age, sex, tumor resection rate, and patient outcome were extracted and studied. The results of the study were compared with the results of similar reports from neighboring countries and other parts of the world.

Results: In this study, 199 primary pediatric tumors were examined. Out of 199 cases, 114 cases were males, and 85 cases were females, and the male/female ratio was 1.34. The most common tumor group in this study was astrocytic tumors (68.3%) and the most common tumor was pilocytic astrocytoma (22.1%). In terms of malignancy, 50.7% of tumors were benign, and 49.3% were malignant. Total resection was done in 46% and subtotal resection in 35%. The mortality rate was found 19.2%. َAmong the remaining cases during follow-up, 76.6% had a good outcome without neurological deficits or mild disability and 23.4% had moderate to severe disability.

Conclusions: The results of the study in terms of pathology and demographic characteristics were mainly similar to other reports. The mean age of patients was lower, and the patients' outcome was better than the other countries in the region.
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http://dx.doi.org/10.1007/s00381-021-05363-wDOI Listing
September 2021

Harnessing polyphenol power by targeting eNOS for vascular diseases.

Crit Rev Food Sci Nutr 2021 Sep 23:1-26. Epub 2021 Sep 23.

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Vascular diseases arise due to vascular endothelium dysfunction in response to several pro-inflammatory stimuli and invading pathogens. Thickening of the vessel wall, formation of atherosclerotic plaques consisting of proliferating smooth muscle cells, macrophages and lymphocytes are the major consequences of impaired endothelium resulting in atherosclerosis, hypercholesterolemia, hypertension, type 2 diabetes mellitus, chronic renal failure and many others. Decreased nitric oxide (NO) bioavailability was found to be associated with anomalous endothelial function because of either its reduced production level by endothelial NO synthase (eNOS) which synthesize this potent endogenous vasodilator from L-arginine or its enhanced breakdown due to severe oxidative stress and eNOS uncoupling. Polyphenols are a group of bioactive compounds having more than 7000 chemical entities present in different cereals, fruits and vegetables. These natural compounds possess many OH groups which are largely responsible for their strong antioxidative, anti-inflammatory antithrombotic and anti-hypersensitive properties. Several flavonoid-derived polyphenols like flavones, isoflavones, flavanones, flavonols and anthocyanidins and non-flavonoid polyphenols like tannins, curcumins and resveratrol have attracted scientific interest for their beneficial effects in preventing endothelial dysfunction. This article will focus on in vitro as well as in vivo and clinical studies evidences of the polyphenols with eNOS modulating activity against vascular disease condition while their molecular mechanism will also be discussed.
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http://dx.doi.org/10.1080/10408398.2021.1971153DOI Listing
September 2021

Ayurveda Rasayana as antivirals and immunomodulators: potential applications in COVID-19.

Environ Sci Pollut Res Int 2021 Sep 7. Epub 2021 Sep 7.

Department of Pharmacognosy, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India.

Coronavirus disease (COVID-19) has been declared as a pandemic by the World Health Organization with rapid spread across 216 countries. COVID-19 pandemic has left its imprints on various health systems globally and caused immense social and economic disruptions. The scientific community across the globe is in a quest for digging the effective treatment for COVID-19 and exploring potential leads from traditional systems of healthcare across the world too. Ayurveda (Indian traditional system of medicine) has a comprehensive aspect of immunity through Rasayana which is a rejuvenation therapy. Here we attempt to generate the potential leads based on the classical text from Ayurveda in general and Rasayana in particular to develop effective antiviral and/or immunomodulator for potential or adjunct therapy in SARS-CoV-2. The Rasayana acts not only by resisting body to restrain or withstand the strength, severity or progression of a disease but also by promoting power of the body to prevent the manifestation of a disease. These Rasayana herbs are common in practice as immunomodulator, antiviral and protectives. The studies on Rasayana can provide an insight into the future course of research for the plausible development of effective management of COVID-19 by the utilization and development of various traditional systems of healthcare. Keeping in view the current pandemic situation, there is an urgent need of developing potential medicines. This study proposes certain prominent medicinal plants which may be further studied for drug development process and also in clinical setup under repurposing of these herbs.
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http://dx.doi.org/10.1007/s11356-021-16280-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422837PMC
September 2021

Himalayan L. Fruit Extract Showed In Vivo Central and Peripheral Analgesic Activity Involving COX-2 and Mu Opioid Receptors.

Plants (Basel) 2021 Aug 16;10(8). Epub 2021 Aug 16.

Department of Neurosurgery, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran 1617763141, Iran.

Analgesic drugs like morphine and non-steroidal anti-inflammatory drugs exhibit several harmful effects. Here, we show for the first time the analgesic activity of L. fruit extract (FPFE) on different analgesic rat models along with the in silico studies of some of the main phytochemicals of this plant. We performed in vivo pain models, along with in silico docking studies against the active site of COX-2 protein and mu-opioid receptors. A significant ( < 0.05) analgesic effect of FPFE was observed, and it was found that rutin has good pose and score as compared to diclofenac and morphinan antagonist (X-ligand), and psoralen has binding affinity almost equal to diclofenac, but a lower binding affinity as compared to rutin. The results proved that fruits have the potential to ameliorate painful conditions.
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http://dx.doi.org/10.3390/plants10081685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398767PMC
August 2021

Curcumin as a Natural Remedy for Atherosclerosis: A Pharmacological Review.

Molecules 2021 Jul 1;26(13). Epub 2021 Jul 1.

Department of Pharmacy, Huadu District People's Hospital, Southern Medical University, Guangzhou 510800, China.

Curcumin, a natural polyphenolic compound present in L. rhizomes, shows potent antioxidant, anti-inflammatory, anti-cancer, and anti-atherosclerotic properties. Atherosclerosis is a comprehensive term for a series of degenerative and hyperplasic lesions such as thickening or sclerosis in large- and medium-sized arteries, causing decreased vascular-wall elasticity and lumen diameter. Atherosclerotic cerebro-cardiovascular disease has become a major concern for human health in recent years due to its clinical sequalae of strokes and heart attacks. Curcumin concoction treatment modulates several important signaling pathways related to cellular migration, proliferation, cholesterol homeostasis, inflammation, and gene transcription, among other relevant actions. Here, we provide an overview of curcumin in atherosclerosis prevention and disclose the underlying mechanisms of action of its anti-atherosclerotic effects.
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http://dx.doi.org/10.3390/molecules26134036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272048PMC
July 2021

Ameliorative potential of against streptozotocin-induced diabetes in rats: biochemical and histopathological studies.

3 Biotech 2021 Jun 2;11(6):309. Epub 2021 Jun 2.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab India.

The study aimed to investigate the acute toxicity, antidiabetic potential (in-vitro and in-vivo) of the (L.) Silva Manso at fraction level. The plant was fractionated into different fractions, i.e., flavonoid fraction (OTFF), tannin fraction (OTTF), saponin fraction (OTSF). In-vitro alpha-amylase inhibition assay revealed that OTFF was found to be more potent than standard Acarbose. The plant fractions were evaluated by MTT assay at different concentrations ranging from 100 to 1000 µg/ml. All the fractions were further evaluated for their safety profile, and the biochemical, hematology and histopathology result exhibits that the OTFF fraction produces mild toxicity at organ level at a concentration of 2000 mg/kg in albino mice. The in-vivo antidiabetic study was carried out on Sprague-Dawley rats using high-fat diet (HFD) feeding streptozotocin (STZ) diabetic model, and the biochemical, histopathology research findings represent that OTFF at a concentration of 500 mg/kg, p.o. was found to be highly significant among all the fractions and found to be more potent than the standard Acarbose. LC-MS characterization of the bioactive fraction OTFF showed the presence of rutin with / 610.52 in 50.50% and Apigenin 7--6'' acetyl-glucoside with / 475.42 in 24.10%; from molecular docking study, it is predicted that the fraction primarily acts as an alpha-amylase inhibitor and PPAR gamma agonist. In conclusion, the plant's OTFF fraction acts as a potential therapeutic agent for Type II diabetes mellitus.
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http://dx.doi.org/10.1007/s13205-021-02811-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172823PMC
June 2021

Targeting the crosstalk between canonical Wnt/β-catenin and inflammatory signaling cascades: A novel strategy for cancer prevention and therapy.

Pharmacol Ther 2021 Apr 27;227:107876. Epub 2021 Apr 27.

Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA. Electronic address:

Emerging scientific evidence indicates that inflammation is a critical component of tumor promotion and progression. Most cancers originate from sites of chronic irritation, infections and inflammation, underscoring that the tumor microenvironment is largely orchestrated by inflammatory cells and pro-inflammatory molecules. These inflammatory components are intimately involved in neoplastic processes which foster proliferation, survival, invasion, and migration, making inflammation the primary target for cancer prevention and treatment. The influence of inflammation and the immune system on the progression and development of cancer has recently gained immense interest. The Wnt/β-catenin signaling pathway, an evolutionarily conserved signaling strategy, has a critical role in regulating tissue development. It has been implicated as a major player in cancer development and progression with its regulatory role on inflammatory cascades. Many naturally-occurring and small synthetic molecules endowed with inherent anti-inflammatory properties inhibit this aberrant signaling pathway, making them a promising class of compounds in the fight against inflammatory cancers. This article analyzes available scientific evidence and suggests a crosslink between Wnt/β-catenin signaling and inflammatory pathways in inflammatory cancers, especially breast, gastrointestinal, endometrial, and ovarian cancer. We also highlight emerging experimental findings that numerous anti-inflammatory synthetic and natural compounds target the crosslink between Wnt/β-catenin pathway and inflammatory cascades to achieve cancer prevention and intervention. Current challenges, limitations, and future directions of research are also discussed.
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http://dx.doi.org/10.1016/j.pharmthera.2021.107876DOI Listing
April 2021

Xanthohumol for Human Malignancies: Chemistry, Pharmacokinetics and Molecular Targets.

Int J Mol Sci 2021 Apr 25;22(9). Epub 2021 Apr 25.

Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA.

Xanthohumol (XH) is an important prenylated flavonoid that is found within the inflorescence of L. (Hop plant). XH is an important ingredient in beer and is considered a significant bioactive agent due to its diverse medicinal applications, which include anti-inflammatory, antimicrobial, antioxidant, immunomodulatory, antiviral, antifungal, antigenotoxic, antiangiogenic, and antimalarial effects as well as strong anticancer activity towards various types of cancer cells. XH acts as a wide ranging chemopreventive and anticancer agent, and its isomer, 8-prenylnaringenin, is a phytoestrogen with strong estrogenic activity. The present review focuses on the bioactivity of XH on various types of cancers and its pharmacokinetics. In this paper, we first highlight, in brief, the history and use of hops and then the chemistry and structure-activity relationship of XH. Lastly, we focus on its prominent effects and mechanisms of action on various cancers and its possible use in cancer prevention and treatment. Considering the limited number of available reviews on this subject, our goal is to provide a complete and detailed understanding of the anticancer effects of XH against different cancers.
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http://dx.doi.org/10.3390/ijms22094478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123270PMC
April 2021

Reactive oxygen species modulators in pulmonary medicine.

Curr Opin Pharmacol 2021 04 17;57:157-164. Epub 2021 Mar 17.

Pharmacognosy Research Laboratories and Herbal Analysis Services, School of Science, University of Greenwich, Central Avenue, Chatham-Maritime, Kent, ME4 4TB, United Kingdom. Electronic address:

Adapted to effectively capture oxygen from inhaled air and deliver it to all other parts of the body, the lungs constitute the organ with the largest surface area. This makes the lungs more susceptible to airborne pathogens and pollutants that mediate pathologies through generation of reactive oxygen species (ROS). One pathological consequence of excessive levels of ROS production is pulmonary diseases that account for a large number of mortality and morbidity in the world. Of the various mechanisms involved in pulmonary disease pathogenesis, mitochondrial dysfunction takes prominent importance. Herein, we briefly describe the significance of oxidative stress caused by ROS in pulmonary diseases and some possible therapeutic strategies.
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http://dx.doi.org/10.1016/j.coph.2021.02.005DOI Listing
April 2021

Epigenetics of glioblastoma multiforme: From molecular mechanisms to therapeutic approaches.

Semin Cancer Biol 2020 Dec 25. Epub 2020 Dec 25.

Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address:

Glioblastoma multiforme (GBM) is the most common form of brain cancer and one of the most aggressive cancers found in humans. Most of the signs and symptoms of GBM can be mild and slowly aggravated, although other symptoms might demonstrate it as an acute ailment. However, the precise mechanisms of the development of GBM remain unknown. Due to the improvement of molecular pathology, current researches have reported that glioma progression is strongly connected with different types of epigenetic phenomena, such as histone modifications, DNA methylation, chromatin remodeling, and aberrant microRNA. Furthermore, the genes and the proteins that control these alterations have become novel targets for treating glioma because of the reversibility of epigenetic modifications. In some cases, gene mutations including P16, TP53, and EGFR, have been observed in GBM. In contrast, monosomies, including removals of chromosome 10, particularly q23 and q25-26, are considered the standard markers for determining the development and aggressiveness of GBM. Recently, amid the epigenetic therapies, histone deacetylase inhibitors (HDACIs) and DNA methyltransferase inhibitors have been used for treating tumors, either single or combined. Specifically, HDACIs are served as a good choice and deliver a novel pathway to treat GBM. In this review, we focus on the epigenetics of GBM and the consequence of its mutations. We also highlight various treatment approaches, namely gene editing, epigenetic drugs, and microRNAs to combat GBM.
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http://dx.doi.org/10.1016/j.semcancer.2020.12.015DOI Listing
December 2020

Fenugreek ( L.) Seeds Dietary Supplementation Regulates Liver Antioxidant Defense Systems in Aging Mice.

Nutrients 2020 Aug 24;12(9). Epub 2020 Aug 24.

Institute of Genetics and Animal Biotechnology Polish Academy of Sciences, 05-552 Magdalenka, Poland.

Fenugreek seeds are widely used in Asia and other places of the world for their nutritive and medicinal properties. In Asia, fenugreek seeds are also recommended for geriatric populations. Here, we evaluated for the first time the effect of fenugreek seed feed supplementation on the liver antioxidant defense systems in aging mice. The study was conducted on 12-months aged mice which were given fenugreek seed dietary supplement. We evaluated the activities of various antioxidant defense enzymes such as superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx), and also estimated the phenolics and free radical scavenging properties in mice liver upon fenugreek supplementation. The estimation of SOD, GPx, and GR activities in aged mice liver revealed a significant ( < 0.01) difference among all the liver enzymes. Overall, this study reveals that fenugreek seed dietary supplementation has a positive effect on the activities of the hepatic antioxidant defense enzymes in the aged mice.
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http://dx.doi.org/10.3390/nu12092552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551560PMC
August 2020

Emerging Therapeutic Promise of Ketogenic Diet to Attenuate Neuropathological Alterations in Alzheimer's Disease.

Mol Neurobiol 2020 Dec 20;57(12):4961-4977. Epub 2020 Aug 20.

King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.

Alzheimer's disease (AD) is a multifactorial and chronic neurodegenerative disorder that interferes with memory, thinking, and behavior. The consumption of dietary fat has been considered a vital factor for AD as this disease is related to blood-brain barrier function and cholesterol signaling. The ε4 allele of apolipoprotein E (APOE4) is a primary genetic risk factor that encodes one of many proteins accountable for the transport of cholesterol and it is deemed as the leading cholesterol transport proteins in the brain. In case of AD development, the causative factor is the high level of serum/plasma cholesterol. However, this statement is arguable and, in the meantime, the levels of brain cholesterol in individuals with AD are extremely inconstant and levels of cholesterol in the brain and serum/plasma of AD individuals do not reflect cholesterol as a risk factor. In fact, APOE4 is neither fundamental nor sufficient for the advancement of AD; it just acts as a synergistic and increases the danger of AD. Another noticeable characteristic of AD is area-specific decreases in the metabolism of brain glucose. It has been found that the brain cells cannot efficiently metabolize fats; hence, they totally rely upon glucose as a vitality substrate. Thus, suppression of glucose metabolism can possess an intense effect on brain actions. Hypometabolism is frequently found in AD and has quite recently achieved impressive consideration as a plausible target for interfering in the progression of the disease. One promising approach is to keep up the normal supply of glucose to the brain with ketone bodies from the ketogenic diet signifies a potential therapeutic agent for AD. Therefore, this review represents the role of ketogenic diets to combat AD pathogenesis by considering the influence of APOE.
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http://dx.doi.org/10.1007/s12035-020-02065-3DOI Listing
December 2020

Structural characterization of Himalayan black rock salt by SEM, XRD and in-vitro antioxidant activity.

Sci Total Environ 2020 Dec 27;748:141269. Epub 2020 Jul 27.

Chrono-Environnement Laboratory, UMR CNRS 6249, Bourgogne Franche-Comté University, F-25030 Besançon Cedex, France.

Salt is an essential component of daily life that balances the physiological functions of the human body as well as other living systems. Different varieties of salts are available in the global market. Out of many salt varieties, Himalayan rock salts have gained tremendous importance among consumers due to its diverse nutritional and medicinal properties. There are two types of Himalayan rock salts. One is the Himalayan pink salt and the other one is Himalayan black salt. Out of the two, the Himalayan pink salt is studied extensively but the black salt is underexplored. In the present study, the Himalayan black rock salt was explored to generate more scientific evidence in terms of its geochemical characterization using FE-SEM, X-ray diffractometry (XRD), elemental content using atomic absorption spectrophotometry (AAS) and in vitro antioxidant activity by different methods for the first time. The study revealed that Himalayan black salt was irregular in shape with a quadrilateral, cubic, irregular crystalline structure. The Himalayan black salt exhibited antioxidant effect and interestingly showed low Na levels than common sea salt and Himalayan pink salt. The Himalayan black salt also contained important minerals like iron, calcium and magnesium which are beneficial to human health thus exhibiting superior characteristics over other conventional table salts.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141269DOI Listing
December 2020

Revisiting the role of brain and peripheral Aβ in the pathogenesis of Alzheimer's disease.

J Neurol Sci 2020 Sep 7;416:116974. Epub 2020 Jun 7.

King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address:

Amyloid beta (Aβ) is an intricate molecule that interacts with several biomolecules and/or produces insoluble assemblies and eventually the nonphysiological depositions of its alternate with normal neuronal conditions leading to Alzheimer's disease (AD). Aβ is formed through the proteolytic cleavage of the amyloid precursor protein (APP). Significant efforts are being made to explore the exact role of Aβ in AD pathogenesis. It is believed that the deposition of Aβ in the brain takes place from Aβ components which are derived from the brain itself. However, recent evidence suggests that Aβ derived also from the periphery and hence the Aβ circulating in the blood is capable of penetrating the blood-brain barrier (BBB) and the role of Aβ derived from the periphery is largely unknown so far. Therefore, Aβ origin determination and the underlying mechanisms of its pathological effects are of considerable interest in exploring effective therapeutic strategies. The purpose of this review is to provide a novel insight into AD pathogenesis based on Aβ in both the brain and periphery and highlight new therapeutic avenues to combat AD pathogenesis.
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http://dx.doi.org/10.1016/j.jns.2020.116974DOI Listing
September 2020

Natural products, PGC-1 , and Duchenne muscular dystrophy.

Acta Pharm Sin B 2020 May 8;10(5):734-745. Epub 2020 Jan 8.

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran 5613156491, Iran.

Peroxisome proliferator-activated receptor (PPAR) is a transcriptional coactivator that binds to a diverse range of transcription factors. PPAR coactivator 1 (PGC-1) coactivators possess an extensive range of biological effects in different tissues, and play a key part in the regulation of the oxidative metabolism, consequently modulating the production of reactive oxygen species, autophagy, and mitochondrial biogenesis. Owing to these findings, a large body of studies, aiming to establish the role of PGC-1 in the neuromuscular system, has shown that PGC-1 could be a promising target for therapies targeting neuromuscular diseases. Among these, some evidence has shown that various signaling pathways linked to PGC-1 are deregulated in muscular dystrophy, leading to a reduced capacity for mitochondrial oxidative phosphorylation and increased reactive oxygen species (ROS) production. In the light of these results, any intervention aimed at activating PGC-1 could contribute towards ameliorating the progression of muscular dystrophies. PGC-1 is influenced by different patho-physiological/pharmacological stimuli. Natural products have been reported to display modulatory effects on PPAR activation with fewer side effects in comparison to synthetic drugs. Taken together, this review summarizes the current knowledge on Duchenne muscular dystrophy, focusing on the potential effects of natural compounds, acting as regulators of PGC-1.
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http://dx.doi.org/10.1016/j.apsb.2020.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276681PMC
May 2020

Molecular Mechanisms of ER Stress and UPR in the Pathogenesis of Alzheimer's Disease.

Mol Neurobiol 2020 Jul 19;57(7):2902-2919. Epub 2020 May 19.

King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.

Alzheimer's disease (AD) is a progressive neurodegenerative disease involving aggregation of misfolded proteins inside the neuron causing prolonged cellular stress. The neuropathological hallmarks of AD include the formation of senile plaques and neurofibrillary tangles in specific brain regions that lead to synaptic loss and neuronal death. The exact mechanism of neuron dysfunction in AD remains obscure. In recent years, endoplasmic reticulum (ER) dysfunction has been implicated in neuronal degeneration seen in AD. Apart from AD, many other diseases also involve misfolded proteins aggregations in the ER, a condition referred to as ER stress. The response of the cell to ER stress is to activate a group of signaling pathways called unfolded protein response (UPR) that stimulates a particular transcriptional program to restore ER function and ensure cell survival. ER stress also involves the generation of reactive oxygen species (ROS) that, together with mitochondrial ROS and decreased effectiveness of antioxidant mechanisms, producing a condition of chronic oxidative stress. The unfolded proteins may not always produce a response that leads to the restoration of cellular functions, but they may also lead to inflammation by a set of different pathways with deleterious consequences. In this review, we extensively discuss the role of ER stress and how to target it using different pharmacological approaches in AD development and onset.
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http://dx.doi.org/10.1007/s12035-020-01929-yDOI Listing
July 2020

Role of Nitric Oxide in Neurodegeneration: Function, Regulation, and Inhibition.

Curr Neuropharmacol 2021 ;19(2):114-126

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran 1435916471, Iran.

Reactive nitrogen species (RNS) and reactive oxygen species (ROS), collectively known as reactive oxygen and nitrogen species (RONS), are the products of normal cellular metabolism and interact with several vital biomolecules including nucleic acid, proteins, and membrane lipids and alter their function in an irreversible manner which can lead to cell death. There is an imperative role for oxidative stress in the pathogenesis of cognitive impairments and the development and progression of neural injury. Elevated production of higher amounts of nitric oxide (NO) takes place in numerous pathological conditions, such as neurodegenerative diseases, inflammation, and ischemia, which occur concurrently with elevated nitrosative/oxidative stress. The enzyme nitric oxide synthase (NOS) is responsible for the generation of NO in different cells by conversion of Larginine (Arg) to L-citrulline. Therefore, the NO signaling pathway represents a viable therapeutic target. Naturally occurring polyphenols targeting the NO signaling pathway can be of major importance in the field of neurodegeneration and related complications. Here, we comprehensively review the importance of NO and its production in the human body and afterwards highlight the importance of various natural products along with their mechanisms against various neurodegenerative diseases involving their effect on NO production.
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http://dx.doi.org/10.2174/1570159X18666200429001549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033982PMC
January 2021

Circadian and sleep dysfunction in Alzheimer's disease.

Ageing Res Rev 2020 07 16;60:101046. Epub 2020 Apr 16.

King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address:

Alzheimer's disease (AD) is a devastating and irreversible cognitive impairment and the most common type of dementia. Along with progressive cognitive impairment, dysfunction of the circadian rhythms also plays a pivotal role in the progression of AD. A mutual relationship among circadian rhythms, sleep, and AD has been well-recommended. The etiopathogenesis of the disturbances of the circadian system and AD share some general features that also unlock the outlook of observing them as a mutually dependent pathway. Indeed, the burden of amyloid β (Aβ), neurofibrillary tangles (NFTs), neuroinflammation, oxidative stress, and dysfunction of circadian rhythms may lead to AD. Aging can alter both sleep timings and quality that can be strongly disrupted in AD. Increased production of Aβ and reduced Aβ clearance are caused by a close interplay of Aβ, sleep disturbance and raised wakefulness. Besides Aβ, the impact of tau pathology is possibly noteworthy to the sleep deprivation found in AD. Hence, this review is focused on the primary mechanistic complexities linked to disruption of circadian rhythms, sleep deprivation, and AD. Furthermore, this review also highlights the potential therapeutic strategies to abate AD pathogenesis.
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http://dx.doi.org/10.1016/j.arr.2020.101046DOI Listing
July 2020

Ethnopharmacological Applications Targeting Alcohol Abuse: Overview and Outlook.

Front Pharmacol 2019 14;10:1593. Epub 2020 Feb 14.

Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrzebiec, Poland.

Excessive alcohol consumption is the cause of several diseases and thus is of a major concern for society. Worldwide alcohol consumption has increased by many folds over the past decades. This urgently calls for intervention and relapse counteract measures. Modern pharmacological solutions induce complete alcohol self-restraint and prevent relapse, but they have many side effects. Natural products are most promising as they cause fewer adverse effects. Here we discuss in detail the medicinal plants used in various traditional/folklore medicine systems for targeting alcohol abuse. We also comprehensively describe preclinical and clinical studies done on some of these plants along with the possible mechanisms of action.
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http://dx.doi.org/10.3389/fphar.2019.01593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034411PMC
February 2020

Modified apple polysaccharide capped gold nanoparticles for oral delivery of insulin.

Int J Biol Macromol 2020 Apr 1;149:976-988. Epub 2020 Feb 1.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India.

The study entailed formulation of gold nanoparticles (AuNPs) upon reduction of chloroauric acid by modified apple polysaccharide (MAP). AuNPs were conjugated with insulin (INS) for its oral delivery to treat type 1 diabetes mellitus (DM). The size of MAP conjugated AuNPs loaded with INS was 124 ± 8.55 nm with zeta potential -10.5 ± 0.54 mV. The animal study carried out in streptozotocin induced rat model revealed that AuNPs conjugated insulin (AuNPs-INS) in high dose caused 3.36 folds decrease in blood glucose level in 240 min, whereas, orally administered INS failed to decrease the blood glucose level. The 28-day study also revealed better improvement in body weight, lipid profile, urea, creatinine and liver parameters in AuNPs-INS (high dose) for which the observed value was close with respect to intraperitoneally administrated insulin followed by medium dose of AuNPs-INS, low dose of AuNPS-INS, AuNPs alone and modified apple polysaccharide.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.01.302DOI Listing
April 2020

Natural products targeting the PI3K-Akt-mTOR signaling pathway in cancer: A novel therapeutic strategy.

Semin Cancer Biol 2019 Dec 19. Epub 2019 Dec 19.

Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA. Electronic address:

The phosphatidylinositol 3-kinase (PI3K)-Akt and the mammalian target of rapamycin (mTOR) represent two vital intracellular signaling pathways, which are associated with various aspects of cellular functions. These functions play vital roles in quiescence, survival, and growth in normal physiological circumstances as well as in various pathological disorders, including cancer. These two pathways are so intimately connected to each other that in some instances these are considered as one unique pathway crucial for cell cycle regulation. The purpose of this review is to emphasize the role of PI3K-Akt-mTOR signaling pathway in different cancer conditions and the importance of natural products targeting the PI3K-Akt-mTOR signaling pathway. This review also aims to draw the attention of scientists and researchers to the assorted beneficial effects of the numerous classes of natural products for the development of new and safe drugs for possible cancer therapy. We also summarize and critically analyze various preclinical and clinical studies on bioactive compounds and constituents, which are derived from natural products, to target the PI3K-Akt-mTOR signaling pathway for cancer prevention and intervention.
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http://dx.doi.org/10.1016/j.semcancer.2019.12.008DOI Listing
December 2019

Targeting Mitogen-Activated Protein Kinases by Natural Products: A Novel Therapeutic Approach for Inflammatory Bowel Diseases.

Curr Pharm Biotechnol 2020 ;21(13):1342-1353

Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

An increase in the prevalence of Inflammatory Bowel Diseases (IBD) as a multifactorial intestinal chronic inflammation as well as the absence of a certain cure, has created an innovative era in the management of IBD by molecule/pathway-based anti-inflammatory approaches. There are credible documentations that demonstrate Mitogen-Activated Protein Kinases (MAPK) acts as IBD regulator. Upon the activation of MAPK signalling pathway, the transcription and expression of various encoding inflammatory molecules implicated in IBD are altered, thereby exacerbating the inflammation development. The current pharmacological management of IBD, including drug and biological therapies are expensive, possess temporary relief and some adverse effects. In this context, a variety of dietary fruits or medicinal herbs have received worldwide attention versus the development of IBD. Infact, natural ingredients, such as Flavaglines, Fisetin, Myricitrin, Cardamonin, Curcumin, Octacosanol and Mangiferin possess protective and therapeutic effects against IBD via modulation of different segments of MAPK signaling pathway. This review paper calls attention to the role of MAPK signaling triggered by natural products in the prevention and treatment of IBD.
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http://dx.doi.org/10.2174/1389201021666191216122555DOI Listing
December 2020

Emerging signal regulating potential of small molecule biflavonoids to combat neuropathological insults of Alzheimer's disease.

Sci Total Environ 2020 Jan 21;700:134836. Epub 2019 Oct 21.

Chrono-Environnement Laboratory, UMR CNRS 6249, Bourgogne Franche-Comté University, Besançon, France. Electronic address:

Alzheimer's disease (AD) is a progressive, chronic and severe neurodegenerative disorder linked with cognitive and memory impairment that eventually lead to death. There are several processes which can cause AD, including mitochondrial dysfunction-mediated oxidative stress (OS), intracellular buildup of hyper-phosphorylated tau as neurofibrillary tangles (NFTs) and excessive buildup of extracellular amyloid beta (Aβ) plaques, and/or genetic as well as the environmental factors. Existing treatments can only provide symptomatic relief via providing temporary palliative therapy which can weaken the rate of AD-associated cognitive decline. Plants are the fundamental building blocks for the environment and produce various secondary metabolites. Biflavonoids are one among such secondary metabolite that possesses the potential to mediate noticeable change in the aggregation of tau, Aβ and also efficiently can decrease the toxic effects of Aβ oligomers in comparison with the monoflavonoid moieties. Nevertheless, the molecular processes remain to be exposed, flavonoids are found to cause a change in the Aβ and tau aggregation pathway to generate non-toxic aggregates. In this review, we discuss the neuroprotective action of small molecule biflavonoid to reduce the neurodegenerative events of AD. Furthermore, this appraisal advances our knowledge to develop potential new targets for the treatment of AD.
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http://dx.doi.org/10.1016/j.scitotenv.2019.134836DOI Listing
January 2020

Targeting BDNF signaling by natural products: Novel synaptic repair therapeutics for neurodegeneration and behavior disorders.

Pharmacol Res 2019 10 20;148:104458. Epub 2019 Sep 20.

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, 6734667149, Kermanshah, Iran.

Neurodegenerative disorders like Alzheimer's disease, Huntington's disease, Parkinson's disease, spinocerebellar ataxias, amyotrophic lateral sclerosis, frontotemporal dementia to prion diseases, Friedreich's ataxia, hereditary spastic paraplegia and optic atrophy type 1, and behavior disorders like neuropsychiatric, hyperactivity and autism spectrum disorders are closely associated with neurobiological deficits. Brain derived neurotrophic factor (BDNF) is an extensively studied neurotrophin. BDNF is essential for neuronal genesis, differentiation, survival, growth, plasticity, synaptic viability and transmission. BDNF has emerged as a promising target for regulating synaptic activity and plasticity. An overview of effects and mechanisms of the natural products targeting BDNF is described. This review is an attempt to enumerate the effects of various natural products on BDNF as a novel therapeutic approach for neurodegenerative and neuropsychiatric disorders.
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http://dx.doi.org/10.1016/j.phrs.2019.104458DOI Listing
October 2019

Phosphodiesterase inhibitors say NO to Alzheimer's disease.

Food Chem Toxicol 2019 Dec 16;134:110822. Epub 2019 Sep 16.

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

Phosphodiesterases (PDEs) consisted of 11 subtypes (PDE1 to PDE11) and over 40 isoforms that regulate levels of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP), the second messengers in cell functions. PDE inhibitors (PDEIs) have been attractive therapeutic targets due to their involvement in diverse medical conditions, e.g. cardiovascular diseases, autoimmune diseases, Alzheimer's disease (AD), etc. Among them; AD with a complex pathology is a progressive neurodegenerative disorder which affect mostly senile people in the world and only symptomatic treatment particularly using cholinesterase inhibitors in clinic is available at the moment for AD. Consequently, novel treatment strategies towards AD are still searched extensively. Since PDEs are broadly expressed in the brain, PDEIs are considered to modulate neurodegenerative conditions through regulating cAMP and cGMP in the brain. In this sense, several synthetic or natural molecules inhibiting various PDE subtypes such as rolipram and roflumilast (PDE4 inhibitors), vinpocetine (PDE1 inhibitor), cilostazol and milrinone (PDE3 inhibitors), sildenafil and tadalafil (PDE5 inhibitors), etc have been reported showing encouraging results for the treatment of AD. In this review, PDE superfamily will be scrutinized from the view point of structural features, isoforms, functions and pharmacology particularly attributed to PDEs as target for AD therapy.
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http://dx.doi.org/10.1016/j.fct.2019.110822DOI Listing
December 2019

Medicinal Plants and Natural Products Used in Cataract Management.

Front Pharmacol 2019 13;10:466. Epub 2019 Jun 13.

Department of Pharmaceutical Botany, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.

Cataract is the leading reason of blindness worldwide and is defined by the presence of any lens opacities or loss of transparency. The most common symptoms of cataract are impaired vision, decreased contrast sensitivity, color disturbance, and glare. Oxidative stress is among the main mechanisms involved in the development of age-related cataract. Surgery through phacoemulsification and intraocular lens implantation is the most effective method for cataract treatment, however, there are chances of serious complications and irreversible loss of vision associated with the surgery. Natural compounds consisting of antioxidant or anti-inflammatory secondary metabolites can serve as potential leads for anticataract agents. In this review, we tried to document medicinal plants and plant-based natural products used for cataract treatment worldwide, which are gathered from available ethnopharmacological/ethnobotanical data. We have extensively explored a number of recognized databases like Scifinder, PubMed, Science Direct, Google Scholar, and Scopus by using keywords and phrases such as "cataract", "blindness", "traditional medicine", "ethnopharmacology", "ethnobotany", "herbs", "medicinal plants", or other relevant terms, and summarized the plants/phytoconstituents that are evaluated in different models of cataract and also tabulated 44 plants that are traditionally used in cataract in various folklore medical practices. Moreover, we also categorized the plants according to scientific studies carried out in different cataract models with their mechanisms of action.
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http://dx.doi.org/10.3389/fphar.2019.00466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585469PMC
June 2019

Oligonucleotide therapy: An emerging focus area for drug delivery in chronic inflammatory respiratory diseases.

Chem Biol Interact 2019 Aug 25;308:206-215. Epub 2019 May 25.

School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar-Delhi G.T. Road (NH-1), Phagwara, 144411, Punjab, India. Electronic address:

Oligonucleotide-based therapies are advanced novel interventions used in the management of various respiratory diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD). These agents primarily act by gene silencing or RNA interference. Better methodologies and techniques are the need of the hour that can deliver these agents to tissues and cells in a target specific manner by which their maximum potential can be reached in the management of chronic inflammatory diseases. Nanoparticles play an important role in the target-specific delivery of drugs. In addition, oligonucleotides also are extensively used for gene transfer in the form of polymeric, liposomal and inorganic carrier materials. Therefore, the current review focuses on various novel dosage forms like nanoparticles, liposomes that can be used efficiently for the delivery of various oligonucleotides such as siRNA and miRNA. We also discuss the future perspectives and targets for oligonucleotides in the management of respiratory diseases.
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http://dx.doi.org/10.1016/j.cbi.2019.05.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094617PMC
August 2019

Nanoparticles and its biomedical applications in health and diseases: special focus on drug delivery.

Environ Sci Pollut Res Int 2020 Jun 11;27(16):19151-19168. Epub 2019 May 11.

Department of Pharmacology, Suez Canal University, Ismailia, Egypt.

Nanotechnology is an emerging technology that deals with nanosized particles possessing crucial research roles and application. Disciplines like chemistry, biology, physics, engineering, materials science, and health sciences provide an accumulated knowledge of nanotechnology. Nonetheless, it has vast submissions precisely in biology, electronics, and medicine. Aimed at drug delivery system, nanoparticles are based on the mechanism of entrapment of the drugs or biomolecules into the interior structure of the particles; another mechanism could be that the drugs or the biomolecules can be absorbed onto the exterior surfaces of the particles. Currently, nanoparticles (NPs) are used in the delivery of drugs, proteins, genes, vaccines, polypeptides, nucleic acids, etc. In recent years, various applications of the drug delivery system via NPs have encountered an enormous position sector like pharmaceutical, medical, biological, and others. Considering the impact of NPs in drug delivery systems, this review focuses on the detailed profile of NPs, its impact on biology and medicine, and their commercialization prospects.
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http://dx.doi.org/10.1007/s11356-019-05211-0DOI Listing
June 2020

Berberine in Cardiovascular and Metabolic Diseases: From Mechanisms to Therapeutics.

Theranostics 2019 16;9(7):1923-1951. Epub 2019 Mar 16.

The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, P.R. China.

Cardiovascular and metabolic diseases (CVMD) are the leading causes of death worldwide, underscoring the urgent necessity to develop new pharmacotherapies. Berberine (BBR) is an eminent component of traditional Chinese and Ayurvedic medicine for more than 2000 years. Recently, BBR has attracted much interest for its pharmacological actions in treating and/or managing CVMD. Recent discoveries of basic, translational and clinical studies have identified many novel molecular targets of BBR (such as AMPK, SIRT1, LDLR, PCSK9, and PTP1B) and provided novel evidences supporting the promising therapeutic potential of BBR to combat CVMD. Thus, this review provides a timely overview of the pharmacological properties and therapeutic application of BBR in CVMD, and underlines recent pharmacological advances which validate BBR as a promising lead drug against CVMD.
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http://dx.doi.org/10.7150/thno.30787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485276PMC
April 2020
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