|
1
|
Azadirachta indica A. Juss Fruit Mesocarp and Epicarp Extracts Induce Antimicrobial and Antiproliferative Effects against Prostate (PC-3), Breast (MCF-7), and Colorectal Adenocarcinoma (Caco-2) Cancer Cell Lines through Upregulation of Proapoptotic Genes. PLANTS 2022; 11:plants11151990. [PMID: 35956468 PMCID: PMC9370754 DOI: 10.3390/plants11151990] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 07/24/2022] [Accepted: 07/28/2022] [Indexed: 11/29/2022]
Abstract
Effective alternative strategies and methodological approaches are critically necessary for cancer prevention and therapy. In this study, we investigated the antitumor potential of neem fruit mesocarp and epicarp extracts. The chemical composition of the derived extracts was characterized using GC–MS. Data were collected on the antimicrobial activity of the extracts in addition to the cytotoxicity effect evaluated against PC-3, MCF-7, and Caco-2 cancer cell lines, compared with the normal Vero cells. Cell-cycle arrest, apoptosis, and expression of apoptosis-related genes were assessed on PC-3 cells. Both extracts had significant antiproliferative effects on all tested cell lines in a dose-dependent manner, with the mesocarp extract being more potent. Both extracts also showed high antibacterial and antifungal activities. These results were related to the chemical constituents of the extracts identified by the GC–MS analysis. The extract of neem fruit mesocarp caused cell-cycle arrest at G2/M phase of PC-3 cells. The cytotoxicity of neem mesocarp extract is strongly correlated with the induction of apoptosis, where it caused downregulation of the antiapoptotic BCL2 gene but upregulation of the proapoptotic P53 and BAX genes. This study showed that neem fruit extract is potential anticancer material in the future.
Collapse
|
|
2
|
Iman M, Taheri M, Bahari Z. The anti-cancer properties of neem ( Azadirachta indica) through its antioxidant activity in the liver: its pharmaceutics and toxic dosage forms. A literature review. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2022; 19:203-211. [PMID: 33964199 DOI: 10.1515/jcim-2021-0009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 04/07/2021] [Indexed: 06/12/2023]
Abstract
OBJECTIVES The neem (Azadirachta indica) have been used in herbal medicine for the treatment of multiple diseases, particularly cancer. The mechanism of anti-cancer properties of neem are far from clear. However, it is well accepted that anti-cancer effects of neem is mediated via its hepatic anti-oxidant activity. In the present review, we are going to classify in vitro and in vivo studies about anti-cancer activity of neem via its hepatic anti-oxidant activity. We also summarize its active ingredients and some therapeutic and toxic dosage forms. METHODS A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar pre-print database using all available MeSH terms for neem, A. indica, anti-cancer, anti-tumor, carcinogen, liver, antioxidant activity, neem ingredients, and glutathione. Electronic database searches combined and duplicates were removed. RESULTS The neem plant have been used in herbal medicine for the treatment of various diseases, particularly cancer. The mechanisms of anti-cancer effects of neem are far from clear. Cancerous cells growth can induce imbalance the oxidant and anti-oxidant activity in various organs particularly in the liver. Therefore, it seems that neem have anti-cancer effects via restore of the antioxidant disturbances close to the control ones in the liver. Additionally, administration of neem extract can induce oncostatic potential via several mechanism including; suppression of the NF-κβ pathway, increased expression of tumor suppressor (such as p53 and pTEN), decreased expression of oncogenes (such as c-Myc), and increased apoptosis in cancerous cells. The median lethal dose (LD50) value for extracts of neem was higher than 2,500 mg/kg. CONCLUSIONS It is suggested that neem plays pivotal role in the prevention and treatment of cancer via its hepatic antioxidant activity. Indeed, application of neem extract can decreased tumor growth via restore of the antioxidant disturbances close to the control ones in the liver.
Collapse
Affiliation(s)
- Maryam Iman
- Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Taheri
- Department of Chemistry, Faculty of Sciences, Golestan University, Gorgan, Iran
| | - Zahra Bahari
- Department of Physiology and Medical Physics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran
- Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
3
|
El-Shall NA, Abd El-Hack ME, Albaqami NM, Khafaga AF, Taha AE, Swelum AA, El-Saadony MT, Salem HM, El-Tahan AM, AbuQamar SF, El-Tarabily KA, Elbestawy AR. Phytochemical control of poultry coccidiosis: a review. Poult Sci 2022; 101:101542. [PMID: 34871985 PMCID: PMC8649401 DOI: 10.1016/j.psj.2021.101542] [Citation(s) in RCA: 105] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 09/20/2021] [Accepted: 10/08/2021] [Indexed: 12/18/2022] Open
Abstract
Avian coccidiosis is a major parasitic disorder in chickens resulting from the intracellular apicomplexan protozoa Eimeria that target the intestinal tract leading to a devastating disease. Eimeria life cycle is complex and consists of intra- and extracellular stages inducing a potent inflammatory response that results in tissue damage associated with oxidative stress and lipid peroxidation, diarrheal hemorrhage, poor growth, increased susceptibility to other disease agents, and in severe cases, mortality. Various anticoccidial drugs and vaccines have been used to prevent and control this disorder; however, many drawbacks have been reported. Drug residues concerning the consumers have directed research toward natural, safe, and effective alternative compounds. Phytochemical/herbal medicine is one of these natural alternatives to anticoccidial drugs, which is considered an attractive way to combat coccidiosis in compliance with the "anticoccidial chemical-free" regulations. The anticoccidial properties of several natural herbal products (or their extracts) have been reported. The effect of herbal additives on avian coccidiosis is based on diminishing the oocyst output through inhibition or impairment of the invasion, replication, and development of Eimeria species in the gut tissues of chickens; lowering oocyst counts due to the presence of phenolic compounds in herbal extracts which reacts with cytoplasmic membranes causing coccidial cell death; ameliorating the degree of intestinal lipid peroxidation; facilitating the repair of epithelial injuries; and decreasing the intestinal permeability induced by Eimeria species through the upregulation of epithelial turnover. This current review highlights the anticoccidial activity of several herbal products, and their other beneficial effects.
Collapse
Affiliation(s)
- Nahed A El-Shall
- Department of Poultry and Fish Diseases, Faculty of Veterinary Medicine, Alexandria University, Edfina, Elbehira 22758, Egypt
| | - Mohamed E Abd El-Hack
- Poultry Department, Faculty of Agriculture, Zagazig University, Zagazig 44511, Egypt
| | - Najah M Albaqami
- Department of Biological Sciences, Zoology, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Asmaa F Khafaga
- Department of Pathology, Faculty of Veterinary Medicine, Alexandria University, Edfina 22758, Egypt
| | - Ayman E Taha
- Department of Animal Husbandry and Animal Wealth Development, Faculty of Veterinary Medicine, Alexandria University, Edfina 22758, Egypt
| | - Ayman A Swelum
- Department of Theriogenology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44511, Egypt
| | - Mohamed T El-Saadony
- Department of Agricultural Microbiology, Faculty of Agriculture, Zagazig University, Zagazig 44511 , Egypt
| | - Heba M Salem
- Department of Poultry Diseases, Faculty of Veterinary Medicine, Cairo University, Giza 12211 , Egypt
| | - Amira M El-Tahan
- Plant Production Department, Arid Lands Cultivation Research Institute, The City of Scientific Research and Technological Applications, Alexandria, Egypt
| | - Synan F AbuQamar
- Department of Biology, College of Science, United Arab Emirates University, Al-Ain,15551, United Arab Emirates
| | - Khaled A El-Tarabily
- Department of Biology, College of Science, United Arab Emirates University, Al-Ain,15551, United Arab Emirates; Harry Butler Institute, Murdoch University, Murdoch, 6150, Western Australia, Australia.
| | - Ahmed R Elbestawy
- Poultry and Fish Diseases Department, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt
| |
Collapse
|
|
4
|
Appiah-Opong R, Tuffour I, Ofori-Attah E, Aning A, Atchoglo P, Danso EA, Ahedor B, Adjei S, Nyarko AK. In Vivo Modulation of Rat Liver Microsomal Cytochrome P450 Activity by Antimalarial, Anti-HIV, and Antituberculosis Plant Medicines. J Evid Based Integr Med 2019; 23:2515690X18810001. [PMID: 30392393 PMCID: PMC6238197 DOI: 10.1177/2515690x18810001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Drug interactions are key reasons for adverse drug reactions and attrition from market. Major infectious diseases causing morbidity/mortality in Ghana are malaria, tuberculosis, and HIV/AIDS. In this study, plant medicines commonly used to treat/manage these diseases in Ghana were investigated for their potential to modulate rat cytochrome P450 enzyme activities. Fluorescence and high-performance liquid chromatography-based assays were used to assess effects of antimalarial plant medicines, Fever (FEV), Mal-TF (MAL), and Kantinka terric (KT); anti-TB medicines, Chestico (CHES), CA + ST Pains + HWNT (TF), and Kantinka herbatic (KHB); and anti-HIV/AIDS medicines, Wabco (WAB), AD + T/AD (LIV) and Kantinka BA (KBA) on rat liver microsomal cytochrome P450 enzyme activities. Effects of medicines on rat biochemical and hematological parameters were also assessed. Generally, the medicines altered microsomal CYP1A1/1A2, CYP2B1/2B2, CYP2C9, and CYP2D6 activities. Only KBA elicited an increase (80%) in CYP1A1/1A2 activity. FEV, MAL, CHES, WAB, and LIV strongly inhibited the enzyme activity. All the medicines significantly inhibited CYP2C9 (24%-80%) activity. CYP2D6 activity increased after treatment with MAL, KBA, LIV, and TF. Also, MAL, WAB, LIV, KHB, and CHES increased CYP2B1/2B2 activity, while KT decrease the activity. Generally, the medicines altered liver function in the rats. Cholesterol levels declined after KBA treatment only. White and red blood cell counts, hemoglobin and hematocrit levels were significantly reduced in KT- and KBA-treated rats. Our results suggest that use of the medicines could have implications for drug interactions and safety, particularly if the medicines are administered over prolonged periods. Further investigations are imperative to establish clinical relevance of these results.
Collapse
|
|
5
|
Chugh NA, Bansal MP, Koul A. The effect of Azadirachta indica Leaf Extract on Early Stages of Chemically Induced Skin Cancer in Mice. ACTA ACUST UNITED AC 2018. [DOI: 10.1080/10496475.2018.1463932] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Affiliation(s)
| | | | - Ashwani Koul
- Department of Biophysics, Panjab University, Chandigarh, India
| |
Collapse
|
|
6
|
Protective effects of Chinese Fenggang zinc selenium tea on metabolic syndrome in high-sucrose-high-fat diet-induced obese rats. Sci Rep 2018; 8:3528. [PMID: 29476111 PMCID: PMC5824815 DOI: 10.1038/s41598-018-21913-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Accepted: 02/02/2018] [Indexed: 02/06/2023] Open
Abstract
The protective effect of zinc selenium tea against metabolic syndrome (MetS) was tested by using a high-sucrose-high-fat diet (HSHFD)-induced MetS model. Fifty Sprague–Dawley rats were randomly divided into five groups: normal diet (C-group), HSHFD (CH-group), HSHFD + green tea (0.24 g/kg/day) (TH-group), HSHFD + low-dose zinc selenium organic tea (0.24 g/kg/day) (ZTHL-group), and HSHFD + high-dose zinc selenium organic tea (1.20 g/kg/day) (ZTHH-group). After 8 weeks, compared to both the C-group and CH-group, the hepatosomatic index (HI) was significantly reduced in the ZTHL-group (p < 0.05). Fasting blood glucose (FBG) levels were highest in the TH-group, followed by the CH-group, then the ZTHL-group, then the ZTHH-group, and finally the C-group. Compared with the CH-group, the serum total cholesterol (TC) and low density lipid-cholesterol (LDL-C) concentrations were significantly lower in the ZTHH-group (p < 0.05). Significant decreases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acids (TBA), alkaline phosphatase (ALP), and direct bilirubin (DBIL) levels were observed in ZTHL-group versus the CH-group (p < 0.05). Serum alpha-L-fucosidase (AFU) levels in the ZTHH-group were lower than in the CH-group (P < 0.01). Histopathological examination of the liver and fat biopsies illustrates that the liver cells showed a decrease in the extent of necrosis and dropsy in the ZTHL-group and ZTHH-group versus the CH-group. Zinc selenium tea showed a protection effect against hepatic damage.
Collapse
|
|
7
|
Kosoko A, Olurinde O, Akinloye O. Doxorubicin induced neuro- and cardiotoxicities in experimental rats: Protection against oxidative damage by Theobroma cacao Stem bark. Biochem Biophys Rep 2017; 10:303-317. [PMID: 28955758 PMCID: PMC5614625 DOI: 10.1016/j.bbrep.2017.01.012] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2016] [Revised: 01/03/2017] [Accepted: 01/27/2017] [Indexed: 12/20/2022] Open
Abstract
80 rats, randomly selected, were divided into 3 treatment groups: pre-, co- and post-treatment; consisting of 6 sub-groups each (5 rats per sub-group): baseline, normal saline (2 mL), α-lipoic acid (20 mg/kg body weight), 200 mg/kg, 400 mg/kg or 800 mg/kg body weight Theobroma cacao stem bark aqueous extract (TCAE). All rats except for baseline group were intoxicated with 20 mg/kg body weight doxorubicin (DOX) intraperitoneally. The animals in pre- or post-treatment group received a single dose of DOX (20 mg/kg body weight) intraperitoneally 24 h before or after 7 days' oral administration with TCAE respectively while those in co-treatment group were co-administered 2.86 mg/kg body weight of DOX with either normal saline, α- lipoic acid or TCAE orally for 7 days. Animals were sacrificed (pre- and post- treatment groups were sacrificed on the ninth day while the co-treatment group sacrificed on the 8th day). Brain and heart tissue samples were harvested for enzyme markers of toxicity, oxidative stress and histopathological examinations. DOX intoxication caused significant decrease in activities of LDH and ACP, and increase in γGT and ALP activities in brain tissues while causing a significant increase in LDH, ACP, γGT activities and decrease in ALP activity in the cardiac tissues. DOX intoxication caused a significant increase in concentrations of H2O2 generated, MDA and PC, XO, MPx and NOX activities with concomitant decrease in CAT, SOD, GPx and GST activities, and in concentrations of GSH, AsA and α-Toc in brain and cardiac tissues. Pre-, co- and post-treatment with TCAE at either 200 mg/kg, 400 mg/kg or 800 mg/kg body weight significantly reversed the oxidative damage to the organs induced by DOX-intoxication. The result affirmed that T. cacao stem bark aqueous extract protected against DOX induced oxidative damage in brain and cardiac tissues of experimental rats.
Collapse
Affiliation(s)
- A.M. Kosoko
- Department of Biochemistry, College of Biosciences (COLBIOS), Federal University of Agriculture, Abeokuta (FUNAAB), Nigeria
| | | | | |
Collapse
|
|
8
|
Bhatia N, Gupta P, Singh B, Koul A. Lycopene Enriched Tomato Extract Inhibits Hypoxia, Angiogenesis, and Metastatic Markers in early Stage N-Nitrosodiethylamine Induced Hepatocellular Carcinoma. Nutr Cancer 2015; 67:1268-75. [DOI: 10.1080/01635581.2015.1087040] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
|
|
9
|
Maver T, Maver U, Stana Kleinschek K, Smrke DM, Kreft S. A review of herbal medicines in wound healing. Int J Dermatol 2015; 54:740-51. [PMID: 25808157 DOI: 10.1111/ijd.12766] [Citation(s) in RCA: 79] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2013] [Revised: 05/17/2014] [Accepted: 05/20/2014] [Indexed: 12/16/2022]
Abstract
Herbs have been integral to both traditional and non-traditional forms of medicine dating back at least 5000 years. The enduring popularity of herbal medicines may be explained by the perception that herbs cause minimal unwanted side effects. More recently, scientists increasingly rely on modern scientific methods and evidence-based medicine to prove efficacy of herbal medicines and focus on better understanding of mechanisms of their action. However, information concerning quantitative human health benefits of herbal medicines is still rare or dispersed, limiting their proper valuation. Preparations from traditional medicinal plants are often used for wound healing purposes covering a broad area of different skin-related diseases. Herbal medicines in wound management involve disinfection, debridement, and provision of a suitable environment for aiding the natural course of healing. Here we report on 22 plants used as wound healing agents in traditional medicine around the world. The aim of this review is therefore to review herbal medicines, which pose great potential for effective treatment of minor wounds.
Collapse
Affiliation(s)
- Tina Maver
- Laboratory for Characterisation and Processing of Polymers, Faculty of Mechanical Engineering, University of Maribor, Maribor, Slovenia
| | - Uroš Maver
- Faculty of Medicine, University of Maribor, Maribor, Slovenia
| | - Karin Stana Kleinschek
- Laboratory for Characterisation and Processing of Polymers, Faculty of Mechanical Engineering, University of Maribor, Maribor, Slovenia
| | | | - Samo Kreft
- Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
| |
Collapse
|
|
10
|
Sophia D, Ragavendran P, Raj CA, Gopalakrishnan VK. Protective effect of Emilia sonchifolia on azaserine-induced pancreatic dysplasia. J Acute Med 2014. [DOI: 10.1016/j.jacme.2014.02.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
|
|
11
|
Arora N, Koul A, Bansal MP. Chemopreventive activity of Azadirachta indica on two-stage skin carcinogenesis in murine model. Phytother Res 2010; 25:408-16. [PMID: 20734334 DOI: 10.1002/ptr.3280] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2009] [Revised: 05/20/2010] [Accepted: 06/29/2010] [Indexed: 12/21/2022]
Abstract
The present study reports the chemopreventive activity of aqueous Azadirachta indica leaf extract (AAILE) in a murine two-stage skin carcinogenesis model. Skin tumors were induced by topical application of 7,12-dimethylbenz(a)anthracene (DMBA) (500 nmol/100 µL for 2 weeks) followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) (1.7 nmol/100 µL of acetone, twice weekly) as a promoter. Male LACA mice were divided into four groups: control, DMBA/TPA, AAILE and AAILE + DMBA/TPA. AAILE was administered orally at a dose level of 300 mg/kg body weight thrice a week for 20 weeks. 100% tumor incidence was observed in the DMBA/TPA treated animals, whereas the AAILE + DMBA treated animals exhibited a tumor incidence of 58.3% only. A significant reduction in the mean tumor burden (54.5%) and mean tumor volume (45.6%) was observed in the mice that received AAILE along with DMBA/TPA. Topical application of DMBA/TPA to the skin resulted in well-developed carcinomas associated with decreased expression of pro-apoptotic protein such as caspase 3 and enhanced expression of antiapoptotic protein such as bcl-2 when compared with the control counterparts. However, adminstration of AAILE inhibited skin carcinogenesis with induction of pro-apoptotic proteins such as bax, caspase 3, caspase 9 and inhibition of antiapoptotic proteins such as bcl-2. These results suggest that the induction of apoptosis may be one of the mechanisms underlying the chemopreventive effects of A. indica.
Collapse
Affiliation(s)
- N Arora
- Department of Biophysics, Panjab University, Chandigarh-160014, India
| | | | | |
Collapse
|
|
12
|
Vellaichamy L, Balakrishnan S, Panjamurthy K, Manoharan S, Alias LM. Chemopreventive potential of piperine in 7,12-dimethylbenz[a]anthracene-induced skin carcinogenesis in Swiss albino mice. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2009; 28:11-18. [PMID: 21783976 DOI: 10.1016/j.etap.2009.01.008] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/09/2008] [Revised: 01/22/2009] [Accepted: 01/23/2009] [Indexed: 05/31/2023]
Abstract
The chemopreventive potential of orally administered piperine was studied in Swiss albino mice against 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin carcinogenesis. The mechanistic pathway for the chemopreventive potential of piperine was evaluated by analysing the status of phase I and phase II detoxification agents, lipid peroxidation by-products and antioxidants during DMBA-induced skin carcinogenesis. Skin squamous cell carcinoma was induced in the shaved back of mice, by painting with DMBA (25μg in 0.1ml acetone/mouse) two times weekly for 8 weeks. We observed severe hyperplasia, dysplasia, and well-differentiated squamous cell carcinoma in the 8th, 10th and 15th week of experimental period respectively in mice treated with DMBA alone. Marked alterations in the status of phase I and phase II detoxification agents, lipid peroxidation by-products and antioxidants were observed in tumor bearing mice. Oral administration of piperine (50mgkg(-1) body weight) by gastric gavage significantly prevented the formation of skin tumors during DMBA-induced mouse skin carcinogenesis. Also, piperine administration brought back the status of phase I and phase II detoxification agents, lipid peroxidation by-products and antioxidants to near normal range in DMBA treated mice. The present study thus demonstrates that piperine has significant suppressing effect on cell proliferation during DMBA-induced mouse skin carcinogenesis. The chemopreventive potential of piperine is probably due to its modulating effect on the status of lipid peroxidation, antioxidants and detoxification agents during DMBA-induced skin carcinogenesis.
Collapse
Affiliation(s)
- Lakshmanan Vellaichamy
- Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608002, Tamil Nadu, India
| | | | | | | | | |
Collapse
|
|
13
|
Gangar SC, Koul A. Azadirachta indica modulates carcinogen biotransformation and reduced glutathione at peri-initiation phase of benzo(a)pyrene induced murine forestomach tumorigenesis. Phytother Res 2008; 22:1229-38. [PMID: 18729244 DOI: 10.1002/ptr.2453] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
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.
Collapse
Affiliation(s)
- Subhash Chander Gangar
- Department of Biophysics, Basic Medical Sciences Block, Panjab University, Chandigarh, India
| | | |
Collapse
|
|
14
|
Rishi P, Rampuria A, Tewari R, Koul A. Phytomodulatory potentials of Aloe vera against Salmonella OmpR-mediated inflammation. Phytother Res 2008; 22:1075-82. [DOI: 10.1002/ptr.2458] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
|
|
15
|
Gangar SC, Sandhir R, Rai DV, Koul A. Preventive effects ofAzadirachta indicaon benzo(a)pyrene-DNA adduct formation in murine forestomach and hepatic tissues. Phytother Res 2006; 20:889-95. [PMID: 16909440 DOI: 10.1002/ptr.1967] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
In the present investigation, the effects of aqueous Azadirachta indica leaf extract (AAILE) on (3)H-benzo(a)pyrene-DNA [(3)H-B(a)P-DNA] adduct formation, the status of biotransformation enzymes and reduced glutathione (GSH) content were evaluated in the forestomach and liver of Balb/c mice. Two weeks of AAILE treatment reduced the (3)H-B(a)P-DNA adduct levels by 31.6% in forestomach tissue. Similarly, (3)H-B(a)P-DNA adduct levels were decreased by 34.7% in the liver of AAILE treated mice compared with their control counterparts. After AAILE treatment, the cytochrome P450 content decreased, whereas the GSH content increased significantly in the hepatic tissue. In the forestomach as well as in the liver, the cytochrome b5 content declined, whereas an increase in glutathione-S-transferase (GST) activity was observed in both tissues. These observations suggested that AAILE may have reduced the metabolic activation of (3)H-B(a)P with enhanced detoxification of its active metabolites, hence the observed decrease in the levels of (3)H-B(a)P-DNA adducts. These molecular and biochemical modulations observed at the initiation phase of carcinogenesis seems to be significant and could be correlated with the chemopreventive effects of A. indica against B(a)P induced forestomach tumorigenesis.
Collapse
Affiliation(s)
- Subhash Chander Gangar
- Department of Biophysics, Basic Medical Sciences Block, Panjab University, Chandigarh 160014, India
| | | | | | | |
Collapse
|
|
16
|
Gangar SC, Sandhir R, Rai DV, Koul A. Modulatory effects of Azadirachta indica on benzo(a)pyrene-induced forestomach tumorigenesis in mice. World J Gastroenterol 2006; 12:2749-55. [PMID: 16718763 PMCID: PMC4130985 DOI: 10.3748/wjg.v12.i17.2749] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2005] [Revised: 09/28/2005] [Accepted: 11/10/2005] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the chemopreventive effects of aqueous Azadirachta indica (A indica) leaf extract (AAILE) against benzo(a)pyrene [B(a)P]-induced forestomach tumorigenesis in Balb/c mice. METHODS Female Balb/c mice were divided into four groups of 10-12 animals each. For induction of forestomach tumors, starting from d 14 of the experi-ment, mice of B(a)P and B(a)P+A indica groups were given intra-gastric instillations of B(a)P (40 mg/kg), twice a week for four weeks. Mice of A indica and B(a)P+A indica groups were orally administered with AAILE (100 mg/kg), two weeks prior to B(a)P instillations till the end of the experiment. After 22 wk of the first B(a)P instillation, mice were sacrificed and the forestomachs were analyzed for development of tumors, scanning electron microscopy (SEM) and histopathology. RESULTS Tumor incidence was observed to be 100% in mice that received only B(a)P. However, treatment with AAILE reduced the tumor incidence by 58.4% as observed in mice of B(a)P+A indica group when compared to that of B(a)P group. Similarly, the tumor burden and multiplicity were seen to decrease by 87.3% and 69.6% respectively in mice of B(a)P+A indica group when compared to those of B(a)P group. Scanning electron microscopy analysis showed that AAILE treatment itself did not cause any abnormalities on the surface architecture of forestomach epithelium. In tumorous forestomach, surface disruption was observed. Over the forestomach tumors of B(a)P group of mice certain rounded structures were seen in addition to closely placed tongue-shaped squamous cells. Interestingly, these rounded structures were not observed in B(a)P + A indica group of mice. Histopathalogically, the tumors were identical and diagnosed to be papillomas. Mice from control and A indica groups of mice did not develop any forestomach tumors and showed normal histo-architecture. CONCLUSION The present data suggest that A indica exerts chemopreventive effects against B(a)P-induced forestomach tumors in murine model. Because of lack of toxicity and ubiquitous bioavailability, A indica may play a promising role in future drug discovery and development as far as chemoprevention of cancer is concerned.
Collapse
Affiliation(s)
- Subhash Chander Gangar
- Department of Biophysics, Basic Medical Sciences Block, Panjab University, Chandigarh, PIN-160014, India
| | | | | | | |
Collapse
|