Publications by authors named "Arun Reddy Ravula"

7 Publications

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Fisetin, potential flavonoid with multifarious targets for treating neurological disorders: An updated review.

Eur J Pharmacol 2021 Sep 10;910:174492. Epub 2021 Sep 10.

Department of Pharmacology, School of Pharmacy, Anurag University (formerly Anurag Group of Institutions), Ghatkesar, Medchal, Hyderabad, Telangana, 500088, India. Electronic address:

Neurodegenerative disorders pose a significant health burden and imprint a debilitative impact on the quality of life. Importantly, aging is intricately intertwined with the progression of these disorders, and their prevalence increases with a rise in the aging population worldwide. In recent times, fisetin emerged as one of the potential miracle molecules to address neurobehavioral and cognitive abnormalities. These effects were attributed to its actions on several macromolecules and multiple molecular mechanisms. Fisetin belongs to a class of flavonoids, which is found abundantly in several fruits and vegetables. Fisetin has manifested several health benefits in preclinical models of neurodegenerative diseases such as Alzheimer's disease, Vascular dementia, and Schizophrenia. Parkinson's disease, Amyotrophic Lateral Sclerosis, Huntington's disease, Stroke, Traumatic Brain Injury (TBI), and age-associated changes. This review aimed to evaluate the potential mechanisms and pharmacological effects of fisetin in treating several neurological diseases. This review also provides comprehensive data on up-to-date recent literature and highlights the various mechanistic pathways pertaining to fisetin's neuroprotective role.
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http://dx.doi.org/10.1016/j.ejphar.2021.174492DOI Listing
September 2021

Correction to: Ocimum Sanctum Linn: A Potential Adjunct Therapy for Hyperhomocysteinemia-Induced Vascular Dementia.

Adv Exp Med Biol 2020 ;1195:C1

Department of Pharmacology, School of Pharmacy, Anurag Group of Institutions, Hyderabad, Telangana, India.

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http://dx.doi.org/10.1007/978-3-030-32633-3_34DOI Listing
January 2020

Behavioral Deficits in Animal Models of Blast Traumatic Brain Injury.

Front Neurol 2020 4;11:990. Epub 2020 Sep 4.

Department of Biomedical Engineering, Center for Injury Biomechanics, Materials and Medicine, New Jersey Institute of Technology, Newark, NJ, United States.

Blast exposure has been identified to be the most common cause for traumatic brain injury (TBI) in soldiers. Over the years, rodent models to mimic blast exposures and the behavioral outcomes observed in veterans have been developed extensively. However, blast tube design and varying experimental parameters lead to inconsistencies in the behavioral outcomes reported across research laboratories. This review aims to curate the behavioral outcomes reported in rodent models of blast TBI using shockwave tubes or open field detonations between the years 2008-2019 and highlight the important experimental parameters that affect behavioral outcome. Further, we discuss the role of various design parameters of the blast tube that can affect the nature of blast exposure experienced by the rodents. Finally, we assess the most common behavioral tests done to measure cognitive, motor, anxiety, auditory, and fear conditioning deficits in blast TBI (bTBI) and discuss the advantages and disadvantages of these tests.
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http://dx.doi.org/10.3389/fneur.2020.00990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500138PMC
September 2020

Ocimum Sanctum Linn: A Potential Adjunct Therapy for Hyperhomocysteinemia-Induced Vascular Dementia.

Adv Exp Med Biol 2020 ;1195:213-225

Department of Pharmacology, School of Pharmacy, Anurag Group of Institutions, Hyderabad, Telangana, India.

Vascular dementia (VaD) is well recognized as the second most familiar form of dementia in the aged population. The present study is aimed to investigate the neuroprotective effects of ethanolic extract of leaves of Ocimum sanctum (EEOS) against hyperhomocysteinemia (HHcy)-induced vascular dementia (VaD) in Wistar rats. HHcy was induced by administering L-methionine (1.7 g/kg, p.o) for 4 weeks. Donepezil (0.1 mg/kg, p.o.) and EEOS (100 mg/kg, 200 mg/kg, 400 mg/kg, p.o.) were administered from the 14 day of L-methionine treatment. The behavioral impairment caused due to HHcy in rats was assessed by the Morris water maze (MWM) and Y-maze tests using a video tracking system. Biochemical estimations and aortic ring assay were also performed followed by a molecular docking analysis of active chemical constituents present in the leaves of Ocimum sanctum Linn. In this study, the EEOS treatment in hyperhomocysteinemic rats has showed significant improvement in spatial learning and working memory performance. The EEOS treatment further increased nitric oxide bioavailability and significantly altered all serum and brain biochemical parameters in a dose-dependent manner. The docking analysis revealed that among all the phytoconstituents of Ocimum sanctum compound (IX), molludistin has showed good inhibitory activity against S-adenosyl homocysteine, thus preventing homocysteine formation and may be responsible for potential effects of EEOS against HHcy-induced VaD. From our results, we conclude that EEOS can be used as a promising adjunct therapy for treatment of HHcy-induced VaD and oxidative stress.
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http://dx.doi.org/10.1007/978-3-030-32633-3_30DOI Listing
September 2020

Synergistic Role of Oxidative Stress and Blood-Brain Barrier Permeability as Injury Mechanisms in the Acute Pathophysiology of Blast-induced Neurotrauma.

Sci Rep 2019 05 22;9(1):7717. Epub 2019 May 22.

Center for Injury Biomechanics, Materials and Medicine (CIBM3), Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, NJ, 07102-1982, USA.

Blast-induced traumatic brain injury (bTBI) has been recognized as the common mode of neurotrauma amongst military and civilian personnel due to an increased insurgent activity domestically and abroad. Previous studies from our laboratory have identified enhanced blood-brain barrier (BBB) permeability as a significant, sub-acute (four hours post-blast) pathological change in bTBI. We also found that NADPH oxidase (NOX)-mediated oxidative stress occurs at the same time post-blast when the BBB permeability changes. We therefore hypothesized that oxidative stress is a major causative factor in the BBB breakdown in the sub-acute stages. This work therefore examined the role of NOX1 and its downstream effects on BBB permeability in the frontal cortex (a region previously shown to be the most vulnerable) immediately and four hours post-blast exposure. Rats were injured by primary blast waves in a compressed gas-driven shock tube at 180 kPa and the BBB integrity was assessed by extravasation of Evans blue and changes in tight junction proteins (TJPs) as well as translocation of macromolecules from blood to brain and vice versa. NOX1 abundance was also assessed in neurovascular endothelial cells. Blast injury resulted in increased extravasation and reduced levels of TJPs in tissues consistent with our previous observations. NOX1 levels were significantly increased in endothelial cells followed by increased superoxide production within 4 hours of blast. Blast injury also increased the levels/activation of matrix metalloproteinase 3 and 9. To test the role of oxidative stress, rats were administered apocynin, which is known to inhibit the assembly of NOX subunits and arrests its function. We found apocynin completely inhibited dye extravasation as well as restored TJP levels to that of controls and reduced matrix metalloproteinase activation in the sub-acute stages following blast. Together these data strongly suggest that NOX-mediated oxidative stress contributes to enhanced BBB permeability in bTBI through a pathway involving increased matrix metalloproteinase activation.
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http://dx.doi.org/10.1038/s41598-019-44147-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531444PMC
May 2019

Effects of fisetin on hyperhomocysteinemia-induced experimental endothelial dysfunction and vascular dementia.

Can J Physiol Pharmacol 2017 Jan 11;95(1):32-42. Epub 2016 Aug 11.

a Department of Pharmacology, Anurag Group of Institutions (Formerly Lalitha College of Pharmacy), Hyderabad, Telangana, India.

This study was designed to investigate the effects of fisetin (FST) on hyperhomocysteinemia (HHcy)-induced experimental endothelial dysfunction (ED) and vascular dementia (VaD) in rats. Wistar rats were randomly divided into 8 groups: control, vehicle control, l-methionine, FST (5, 10, and 25 mg/kg, p.o.), FST-per se (25 mg/kg, p.o.), and donepezil (0.1 mg/kg, p.o.). l-Methionine administration (1.7 g/kg, p.o.) for 32 days induced HHcy. ED and VaD induced by HHcy were determined by vascular reactivity measurements, behavioral analysis using Morris water maze and Y-maze, along with a biochemical and histological evaluation of thoracic aorta and brain tissues. Administration of l-methionine developed behavioral deficits; triggered brain lipid peroxidation (LPO); compromised brain acetylcholinesterase activity (AChE); and reduced the levels of brain superoxide dismutase (SOD), brain catalase (CAT), brain reduced glutathione (GSH), and serum nitrite; and increased serum homocysteine and cholesterol levels. These effects were accompanied by decreased vascular NO bioavailability, marked intimal thickening of the aorta, and multiple necrotic foci in brain cortex. HHcy-induced alterations in the activities of SOD, CAT, GSH, AChE, LPO, behavioral deficits, ED, and histological aberrations were significantly attenuated by treatment with fisetin in a dose-dependent manner. Collectively, our results indicate that fisetin exerts endothelial and neuroprotective effects against HHcy-induced ED and VaD.
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http://dx.doi.org/10.1139/cjpp-2016-0147DOI Listing
January 2017

Highly sensitive LC-MS/MS-ESI method for determination of phenelzine in human plasma and its application to a human pharmacokinetic study.

J Chromatogr B Analyt Technol Biomed Life Sci 2016 Jun 9;1022:126-132. Epub 2016 Apr 9.

University college of Pharmaceutical Sciences, Andhra University, Visakhapatnam 530 003, A.P, India.

A selective, sensitive and rapid LC-MS/MS method has been developed and validated for quantification of the phenelzine (PZ) in 200μL of human plasma using hydroxyzine (HZ) as an internal standard (IS) as per regulatory guidelines. The sample preparation involved the derivatization of PZ using pentaflurobenzaldehyde followed by solid phase extraction process to extract PZ and HZ from human plasma. LC-MS/MS was operated under the multiple reaction-monitoring mode (MRM) using the electro spray ionization technique in positive ion mode and the transitions of m/z 305.1→105.1 and m/z 375.3→201.1 were used to measure the derivative of PZ and IS, respectively. The total run time was 3.5min and the elution of PZ and HZ occurred at 2.53, and 1.92min, respectively; this was achieved with a mobile phase consisting of 10mM ammonium acetate: acetonitrile (20:80, v/v) at a flow rate of 1.0mL/min on an Ace C18 column with a split ratio of 70:30. The developed method was validated in human plasma with a lower limit of quantitation 0.51ng/mL. A linear response function was established for the range of concentrations 0.51-25.2ng/mL (r>0.995) for PZ. The intra- and inter-day precision values met the acceptance criteria. PZ was stable in the battery of stability studies viz., stock solution, bench-top, auto-sampler, long-term and freeze/thaw cycles. The developed assay method was applied to an oral bioequivalence study in humans.
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http://dx.doi.org/10.1016/j.jchromb.2016.04.006DOI Listing
June 2016
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