Papers by Richard Jayaraj
Copious experimental and postmortem studies have shown that oxidative stress mediated degeneratio... more Copious experimental and postmortem studies have shown that oxidative stress mediated degeneration of nigrostriatal dopaminergic neurons underlies Parkinson's disease (PD) pathology. CNB-001, a novel pyrazole derivative of curcumin, has recently been reported to possess various neuroprotective properties. This study was designed to investigate the neuroprotective mechanism of CNB-001 in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rodent model of PD. Administration of MPTP (30 mg/kg for four consecutive days) exacerbated oxidative stress and motor impairment and reduced tyrosine hydroxylase (TH), dopamine transporter, and vesicular monoamine transporter 2 (VMAT2) expressions. Moreover, MPTP induced ultrastructural changes such as distorted cristae and mitochondrial enlargement in substantia nigra and striatum region. Pretreatment with CNB-001 (24 mg/kg) not only ameliorated behavioral anomalies but also synergistically enhanced monoamine transporter expressions and cosseted mitochondria by virtue of its antioxidant action. These findings support the neuroprotective property of CNB-001 which may have strong therapeutic potential for treatment of PD.
Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder after A... more Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Etiology of PD is progressive loss of dopaminergic neurons in Substantia nigra pars compacta (SNpc). One of the pathological hallmarks of PD is the presence of intracellular proteinaceous substances termed 'Lewy bodies' composed of aggregated alpha-synuclein which is responsible for its toxic effect on SNpc. Hence any therapeutic target which blocks α-synuclein aggregation will provide a new channel to cure PD. Objective: The aim of the present study is to identify potent inhibitors (ligands) which binds to active site of α-synuclein and prevents selfassociation. Methods: In this study, insilico molecular docking was done against α-synuclein using five plant derived compounds namely (a) stimovul (b) 7,8dihydroxycoumarin, (c) etorphine (d) propoxyphene and (e) pentazdine. These compounds were analyzed for their Lipinski and ADMET properties using Accelrys Discovery studio 3.5. Molecular docking was performed between ligand and protein using Lead IT. Results: Results revealed that the best fit ligands against active site of α-synuclein were identified as Stimovul with a docking score of -4.5122 and the interacting amino acids were found to be SER 87 and VAL 95 followed by other compounds. Conclusion: These compounds which have the ability to bind to α-Synuclein insilico can be further developed using invitro and in vivo studies as a potent anti-parkinson drug.
The toxicity of mercury in humans and animals are well established and this depends greatly on th... more The toxicity of mercury in humans and animals are well established and this depends greatly on the mercuric compounds. In this study Thespesia populnea has been investigated for its possible protective role in mercury induced cellular damage using Swiss albino mice. The liver marker enzymes SGPT and SGOT exhibited higher activity and the antioxidant enzymes CAT, GPx and GST in mercuric chloride [HgCl2] treated animals were lower. Liver histopathology showed that Thespesia populnea bark extract inhibited these amendments, had reduced fat cyst formation and developed binucleated cells induced by HgCl2 intoxication. From these results we conclude that enhanced levels of antioxidant enzymes and reduced amount of serum amino transaminase are responsible for the major protecting mechanisms of T. populnea bark extract in mercury induced oxidative stress in liver.
Chemico-Biological Interactions
Parkinson's disease (PD) is characterized by the ... more Parkinson's disease (PD) is characterized by the progressive degeneration via apoptosis of nigrostriatal dopaminergic neurons associated with inflammation, resulting in behavioral anomalies. Therefore, an anti-apoptotic and anti-inflammatory regimen may be useful in treatment of PD. CNB-001, a novel pyrazole derivative of curcumin and cyclohexyl bisphenol A has superior biological properties than its parental compounds. The present study utilizes a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD to investigate anti-inflammatory and anti-apoptotic mediated neuroprotection of CNB-001. The administration of MPTP (30 mg/kg for four successive days) significantly induced motor impairments as determined by behavioral studies (narrow beam test, catalepsy and akinesia), lowered dopamine levels and up-regulated the expressions of the inflammatory and apoptotic markers (tumor necrosis factor-alpha, interleukin-1β, interleukin-6, inducible nitric oxide synthase, glial fibrillary acidic protein, cyclooxygenase-2 and Bax). Moreover, MPTP treatment attenuated Bcl-2 and nigrostriatal dopamine transporter expression and also increased total nitrite and citrulline levels in comparison to the control group. However, co-treatment with CNB-001 significantly attenuated motor impairments and pathological changes caused by MPTP administration. Collectively, our results demonstrate that CNB-001 is neuroprotective through its anti-inflammatory and anti-apoptotic properties. Thus, CNB-001 has potential to be further developed as a therapeutic candidate for treatment of PD.
ABSTRACT Purpose Ulcerative colitis (UC) is associated with tainted neutrophil infiltration, dere... more ABSTRACT Purpose Ulcerative colitis (UC) is associated with tainted neutrophil infiltration, deregulated pro-inflammatory mediators, characterized by severe oxidative stress of the intestine. In the present study, an effort was made to evaluate the effect of methanolic fractions of Eupatorium triplinerve (E. triplinerve) (ET) on acetic acid induced ulcerative colitis in male adult mice. Methods Colitis in mice was induced with 3.0% acetic acid (v/v) in saline via rectal route. Pre-intervention with E. triplinerve extract (100 mg and 200 mg kg−1 body weight, oral) and reference drug ranitidine (50 mg kg−1 body weight used as reference, oral) 4 days before induction of colitis and was extended up to 8 days. Results The phase of inflammation before E. triplinerve extract pre-treatment significantly showed attenuated macroscopic damage, argyrophilic nuclear organization regions (AgNORs) count and histological changes. Similarly, extract also effectively detracts the activity of both Myeloperoxidase (MPO) and Malondialdehyde (MDA) levels by enhancing the cellular antioxidant enzyme levels (Glutathione-s-transferase [GST], Glutathione peroxidise [GPx] and Catalase [CAT]) at the site of ulceration. Conclusions The E. triplinerve based therapy resolved that some constituents in extract have an antiulcer effect against UC at colon specific area through its inviolable radical scavenging activity.
The prevalence of Parkinson's disease (PD), the second most common neurodegenerative disorder, is... more The prevalence of Parkinson's disease (PD), the second most common neurodegenerative disorder, is increasing day by day and poses a great threat to the elderly population. Its main neuropathological feature is the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). However, the pathogenesis of PD is not understood fully. Clinical, experimental, microanatomic, and biochemical evidence suggest PD involves multifactorial oxidative neurodegeneration. The SNpc is uniquely vulnerable to oxidative damage, having a high content of oxidizable dopamine, neuromelanin, polyunsaturated fatty acids, and iron, and relatively low antioxidant complement with high metabolic rate. The aim of this review is to bring out the incidence of PD in India compared to that of Europe. Since ancient times plants have been valued for their medicinal properties, and many cultures still rely on plants as their major source of medicine. In this review we discuss the role of Indian medicinal plants in countering free-radical damage and also give you a glimpse about the clinical and pathological features of PD, available treatments, their drawbacks, and future challenges to overcome PD. KEY WORDS: Parkinson's disease, oxidative stress, herbs Parkinson disease and oxidative stress Volume 1, Number 2, 2012 of cellular dysfunction.
Parkinson disease is the second most increasing neurodegenerative disorder. Benchmark studies pro... more Parkinson disease is the second most increasing neurodegenerative disorder. Benchmark studies proved that presence of Lewy body formation with dense Alpha-Synuclein population and its selfaggregation is responsible for its toxic effect on dopaminergic neuronal cells. This Insilico study investigates the inhibitory effects of Resveratrol, Resorcinol, Epigallocatechin, Trolox and Rosmarinic acid against alpha-synuclein self-aggregation and the study showed positive inhibitory results against alpha-synuclein.
BioMed research international, 2014
Copious experimental and postmortem studies have shown that oxidative stress mediated degeneratio... more Copious experimental and postmortem studies have shown that oxidative stress mediated degeneration of nigrostriatal dopaminergic neurons underlies Parkinson's disease (PD) pathology. CNB-001, a novel pyrazole derivative of curcumin, has recently been reported to possess various neuroprotective properties. This study was designed to investigate the neuroprotective mechanism of CNB-001 in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rodent model of PD. Administration of MPTP (30 mg/kg for four consecutive days) exacerbated oxidative stress and motor impairment and reduced tyrosine hydroxylase (TH), dopamine transporter, and vesicular monoamine transporter 2 (VMAT2) expressions. Moreover, MPTP induced ultrastructural changes such as distorted cristae and mitochondrial enlargement in substantia nigra and striatum region. Pretreatment with CNB-001 (24 mg/kg) not only ameliorated behavioral anomalies but also synergistically enhanced monoamine transporter expressions and cosseted mitochondria by virtue of its antioxidant action. These findings support the neuroprotective property of CNB-001 which may have strong therapeutic potential for treatment of PD.
New strategies for the prevention of colon cancer persists a crucial need. However, resistance to... more New strategies for the prevention of colon cancer persists a crucial need. However, resistance to current
chemopreventive drugs is relatively prevalent in colon carcinogenesis. For this intent, a chemopreventive
study was acquitted to elucidate the probable effect of taxifolin (TAX) against 1,2-dimethylhydrazine
(DMH) induced colon carcinogenesis in mice and to evaluate its efficacy with 5-fluorouracil (5-FU) drug
control. Swiss Albino mice were intended for colon carcinogenesis received subcutaneous injections of
DMH (20 mg/kg bw., sc) once a week for 15 weeks and were treated with TAX (4 g/kg bw, op) and 5-FU
drug control (10 mg/kg bw., op) for the entire study period. Our results unveil that mice administered with
TAX significantly modulates DMH induced histological alterations (ACF, AgNORs, and mucin depletion).
Moreover, TAX treatment also inhibits DMH mediated oxidative damage by diminishing tissue lipid
peroxidation (MDA, MPO and CD) accompanied by enhanced activities of enhanced activities of free
radical metabolizing enzymes (SOD, CAT, GPx, GR, GSH, vitamin A, C and E). Apoptotic and proliferating
cell nuclear antigen (PCNA) findings also revealed that treatment with TAX substantially regulates cell
proliferation through the increased extent of DNA fragmentation. The incidence of colon cancer in TAX
treated mice was significantly reduced when compared to that of 5-FU control. Our findings concluded
that taxifolin act as an effective chemopreventive agent against colon carcinogenesis by its virtue of
antioxidant mediated apoptosis and anti-proliferative activities.
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Papers by Richard Jayaraj
chemopreventive drugs is relatively prevalent in colon carcinogenesis. For this intent, a chemopreventive
study was acquitted to elucidate the probable effect of taxifolin (TAX) against 1,2-dimethylhydrazine
(DMH) induced colon carcinogenesis in mice and to evaluate its efficacy with 5-fluorouracil (5-FU) drug
control. Swiss Albino mice were intended for colon carcinogenesis received subcutaneous injections of
DMH (20 mg/kg bw., sc) once a week for 15 weeks and were treated with TAX (4 g/kg bw, op) and 5-FU
drug control (10 mg/kg bw., op) for the entire study period. Our results unveil that mice administered with
TAX significantly modulates DMH induced histological alterations (ACF, AgNORs, and mucin depletion).
Moreover, TAX treatment also inhibits DMH mediated oxidative damage by diminishing tissue lipid
peroxidation (MDA, MPO and CD) accompanied by enhanced activities of enhanced activities of free
radical metabolizing enzymes (SOD, CAT, GPx, GR, GSH, vitamin A, C and E). Apoptotic and proliferating
cell nuclear antigen (PCNA) findings also revealed that treatment with TAX substantially regulates cell
proliferation through the increased extent of DNA fragmentation. The incidence of colon cancer in TAX
treated mice was significantly reduced when compared to that of 5-FU control. Our findings concluded
that taxifolin act as an effective chemopreventive agent against colon carcinogenesis by its virtue of
antioxidant mediated apoptosis and anti-proliferative activities.
chemopreventive drugs is relatively prevalent in colon carcinogenesis. For this intent, a chemopreventive
study was acquitted to elucidate the probable effect of taxifolin (TAX) against 1,2-dimethylhydrazine
(DMH) induced colon carcinogenesis in mice and to evaluate its efficacy with 5-fluorouracil (5-FU) drug
control. Swiss Albino mice were intended for colon carcinogenesis received subcutaneous injections of
DMH (20 mg/kg bw., sc) once a week for 15 weeks and were treated with TAX (4 g/kg bw, op) and 5-FU
drug control (10 mg/kg bw., op) for the entire study period. Our results unveil that mice administered with
TAX significantly modulates DMH induced histological alterations (ACF, AgNORs, and mucin depletion).
Moreover, TAX treatment also inhibits DMH mediated oxidative damage by diminishing tissue lipid
peroxidation (MDA, MPO and CD) accompanied by enhanced activities of enhanced activities of free
radical metabolizing enzymes (SOD, CAT, GPx, GR, GSH, vitamin A, C and E). Apoptotic and proliferating
cell nuclear antigen (PCNA) findings also revealed that treatment with TAX substantially regulates cell
proliferation through the increased extent of DNA fragmentation. The incidence of colon cancer in TAX
treated mice was significantly reduced when compared to that of 5-FU control. Our findings concluded
that taxifolin act as an effective chemopreventive agent against colon carcinogenesis by its virtue of
antioxidant mediated apoptosis and anti-proliferative activities.