Chemopreventive potential of Azadirachta indica (Neem) leaf extract in murine carcinogenesis model systems

Dasgupta, Trisha; Banerjee, Sagarika; Yadava, Pramod Kumar; Rao, A.R.

doi:10.1016/j.jep.2003.12.004

Cited by 89 publications

(65 citation statements)

References 43 publications

(38 reference statements)

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“…However, a significant decrease was observed in LDH activity in DMN-injected rats that were simultaneously treated with ethanolic leaf extracts of Vernonia amygdalina compared with DMNfibrotic rats suggesting the modulatory effects of Vernonia amygdalina against loss of membrane integrity. Similar effects of Azadirachta indica (Neem) leaf extract in reducing the activity of LDH in hepatic tissue of mice treated with benzo(a)pyrene and 7,12-dimethyl benz(a)anthracene (DMBA) have previously been reported (Dasgupta et al 2004, Ganger et al 2006). Muthulingam et al (2010) also reported decreased LDH activity in a study on the antihepatotoxic efficacy of Indigofera tinctoria on paracetamolinduced liver damage in rats.…”

Section: Discussionsupporting

confidence: 62%

Dimethylnitrosamine (DMN)-induced fibrotic rats: effect of Vernonia amygdalina on extracellular matrix and Hepatic/lysosomal integrity

Usunobun

Okolie

2016

IJPT

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Background: Hepatic fibrosis is the accumulation of extracellular matrix protein, or scar, in response to acute or chronic liver injury. This study investigated the effect of ethanolic leaf extract of Vernonia amygdalina on extracellular matrix protein: hyaluronic acid (HA), liver synthetic molecules: total protein (TP), albumin (ALB), total bilirubin (TB) as well as lysosomal membrane stability: acid phosphatase (ACP) in dimethylnitrosamine (DMN)-induced fibrotic rats. Methods: Wistar albino male rats were intraperitoneally injected with 10 mg/kg DMN on first three days a week for two weeks. Ethanolic leaf extracts of Vernonia amygdalina (200 mg /kg) was administered simultaneously by oral gavage daily for two weeks. All rats were sacrificed after 24 hours of last administration by cardiac puncture, and blood collected from the ocular vein. Analysis of serum ACP and LDH activities with those of the concentrations of HA, ALB, TP and TB were carried out. Results: Administration of DMN to rats significantly increased HA and TB concentration and the activities of ACP and LDH (p<0.05) in the serum while it significantly reduced (p<0.05) serum TP and ALB concentrations when compared with controls. However, simultaneous administration of ethanolic leaf extracts of Vernonia amygdalina with DMN significantly (p<0.05) reversed these changes. Conclusion: This study shows that Vernonia amygdalina possesses hepatoprotective, lysosomal membrane stabilizing and anti-fibrotic properties may be due to its antioxidant and phytochemical constituents.

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Section: Discussionsupporting

confidence: 62%

Dimethylnitrosamine (DMN)-induced fibrotic rats: effect of Vernonia amygdalina on extracellular matrix and Hepatic/lysosomal integrity

Usunobun

Okolie

2016

IJPT

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“…Moreover, its significant chemopreventive potential against certain malignancies, as documented by several recent studies Dasgupta et al, 2004;Koul et al, 2006b) have attracted the attention of the scientific community especially in the past few years. Recently, the chemopreventive effects of AAILE against B(a)P induced forestomach tumorigenesis were reported in female Balb/c mice.…”

Section: Discussionmentioning

confidence: 99%

Azadirachta indica modulates carcinogen biotransformation and reduced glutathione at peri‐initiation phase of benzo(a)pyrene induced murine forestomach tumorigenesis

Gangar

Koul

2008

Phytotherapy Research

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The present study evaluated the effects of aqueous Azadirachta indica leaf extract (AAILE) on the activities of certain phase I (cytochrome P450, cytochrome b(5) and aryl hydrocarbon hydroxylase) as well as phase II (glutathione-S-transferase and UDP-glucuronosyl transferase) biotransformation enzymes; and reduced glutathione (GSH) (in forestomach and hepatic tissues) during/after intra-gastric instillations of B(a)P in murine forestomach tumorigenesis bioassay protocol. The activities of phase I biotransformation enzymes were found to increase, whereas a decrease in GSH content as well as glutathione-S-transferase was observed in mice receiving only B(a)P during as well as 2 weeks after B(a)P instillations. The activity of UDP-glucuronosyltransferase decreased during B(a)P instillations, whereas after the latter, the activity increased when compared with the control mice. However, in mice that received AAILE along with B(a)P instillations, a decrease in phase I enzymes was accompanied by an increase in phase II enzymes as well as GSH contents. Only AAILE treatment reduced the activities of phase I biotransformation enzymes and enhanced the GSH contents as well as the activities of phase II enzymes. Observations of the present study seem to be quite significant and (when taken together with our earlier findings) provides evidence for A. indica mediated modulation of the peri-initiation phase of the process of forestomach tumorigenesis.

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“…Neem tree constituents exhibit various multi-targeted biological activities, such as antibacterial [63], hypoglycemic [39], anti-ulcer [45], antimalarial [33], hepatoprotective [8], spermicidal [4], anti-inflammatory [9,44,66], chemopreventive [15,62], and chemotherapeutic [23,24,41] properties. Additionally, the nutritional potential of neem oil was evaluated by Rukimini [50].…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory, pro-apoptotic, and anti-proliferative effects of a methanolic neem (Azadirachta indica) leaf extract are mediated via modulation of the nuclear factor-κB pathway

et al. 2010

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Azadirachta indica (neem tree) is used in traditional Indian medicine for its pharmacological properties including cancer prevention and treatment. Here, we studied a neem extract's anti-inflammatory potential via the nuclear factor-jB (NF-jB) signaling pathway, linked to cancer, inflammation, and apoptosis. Cultured human leukemia cells were treated with a methanolic neem leaf extract with or without tumor necrosis factor (TNF)-a stimulation. Inhibition of NF-jB activity was demonstrated by luciferase assay and electrophoretic mobility shift assay (EMSA). Inhibition of viability by neem extracts was assessed by luminescent assays. Western blot analysis allowed assessing the inhibitory effect of the neem extract on TNF-a-induced degradation of inhibitor of jB (IjB) and nuclear translocation of the NF-jB p50/p65 heterodimer. Inhibition of IjB kinase (IKK) activity was shown as well as the effect of neem extract on the induction of apoptotic cell death mechanisms by nuclear fragmentation analysis and flow cytometry analysis. In conclusion, our data provide evidence for a strong effect of the neem extract on proinflammatory cell signaling and apoptotic cell death mechanisms, contributing to a better understanding of the mechanisms triggered by Azadirachta indica.

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Chemopreventive potential of Azadirachta indica (Neem) leaf extract in murine carcinogenesis model systems

Cited by 89 publications

References 43 publications

Dimethylnitrosamine (DMN)-induced fibrotic rats: effect of Vernonia amygdalina on extracellular matrix and Hepatic/lysosomal integrity

Dimethylnitrosamine (DMN)-induced fibrotic rats: effect of Vernonia amygdalina on extracellular matrix and Hepatic/lysosomal integrity

Azadirachta indica modulates carcinogen biotransformation and reduced glutathione at peri‐initiation phase of benzo(a)pyrene induced murine forestomach tumorigenesis

Anti-inflammatory, pro-apoptotic, and anti-proliferative effects of a methanolic neem (Azadirachta indica) leaf extract are mediated via modulation of the nuclear factor-κB pathway

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