The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Jinyong Peng - One of the best experts on this subject based on the ideXlab platform.
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protective effects of dioscin against fructose induced renal damage via adjusting sirt3 mediated oxidative stress fibrosis lipid metabolism and inflammation
Toxicology Letters, 2018Co-Authors: Yujie Qiao, Lianhong Yin, Xufeng Tao, Xu Han, Zeyao Tang, Kexin Liu, Jinyong PengAbstract:In the present work, the effects and possible mechanisms of dioscin, one natural product from the famous vegetable Dioscoreae rhizoma (Shanyao in Chinese), against high fructose-induced renal injury in rats were tested. The results showed that dioscin significantly restored fructose-induced renal injury by decreasing the levels of Cr, BUN, and rehabilitating histopathological changes. In addition, dioscin markedly adjusted the levels of MDA, SOD and GSH-Px, reduced ROS level in renal tissue, and decreased the levels of TG, FFA, α-SMA and COL1A. Mechanistic study showed that dioscin significantly up-regulated the expression levels of Sirt3, SOD2, and then suppressed inflammation by decreasing the expression levels of NF-kB, HMGB1, c-Jun, c-Fos, COX2, TNF-α, IL-1β and IL-6. Furthermore, dioscin-caused high levels of Sirt3 and SOD2 attenuated oxidative stress by regulating the expression levels of Nrf2, GST, Keap1, regulated lipid metabolism by controlling the expression levels of SREBP-1c, SCD-1, FASn, ACC, CPT1, and adjusted TGF-β1/Smad signal to inhibit renal fibrosis. In summary, dioscin showed protective effects against fructose-induced renal damage via adjusting Sirt3-mediated oxidative stress, renal fibrosis, lipid metabolism and inflammation, which should be considered as one candidate to treat renal injury in the future. We also suggest that the patients with renal injury can take more Shanyao for the therapy and treatment.
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protective effect of dioscin against thioacetamide induced acute liver injury via fxr ampk signaling pathway in vivo
Biomedicine & Pharmacotherapy, 2018Co-Authors: Lingli Zheng, Lina Xu, Yan Qi, Hua Li, Youwei Xu, Jinyong PengAbstract:Abstract Our previous works showed that dioscin, a natural product, could protect liver from acute liver damages induced by dimethylnitrosamine, ethanol, carbon tetrachloride and acetaminophen. However, the effect of dioscin on thioacetamide (TAA)-induced acute liver injury still remained unknown. The purpose of this study was to investigate whether dioscin confers a protective effect against TAA-induced acute liver injury in rats and mice. The results showed that dioscin decreased the serum levels of ALT, AST, and rehabilitated histopathological changes compared with the model groups. In addition, dioscin obviously increased the levels of GSH, GSH-Px, SOD, and significantly reduced MDA levels compared with the model groups. Mechanistic study showed that dioscin significantly up-regulated the expression levels of FXR, p-AMPKα, and then increased the expression levels of Nrf2, HO-1, NQO-1, GCLM and GST. Furthermore, dioscin obviously down-regulated the expression levels of NF-κB (p65), ICAM-1, HMGB1, COX-2, TNF-α, IL-1β and IL-6. Taken together, dioscin showed protective effect against TAA-induced acute liver injuries in rats and mice and the effects might be obtained through inhibiting oxidative stress and inflammation via FXR/AMPK signal pathway. These findings provided a new insight on the role of doscin in the treatment of acute liver injury.
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dioscin alleviates dimethylnitrosamine induced acute liver injury through regulating apoptosis oxidative stress and inflammation
Environmental Toxicology and Pharmacology, 2016Co-Authors: Weixin Zhang, Lingli Zheng, Lianhong Yin, Xufeng Tao, Xu Han, Changyuan Wang, Jinyong PengAbstract:In our previous study, the effects of dioscin against alcohol-, carbon tetrachloride- and acetaminophen-induced liver damage have been found. However, the activity of it against dimethylnitrosamine (DMN)-induced acute liver injury remained unknown. In the present study, dioscin markedly decreased serum ALT and AST levels, significantly increased the levels of SOD, GSH-Px, GSH, and decreased the levels of MDA, iNOS and NO. Mechanism study showed that dioscin significantly decreased the expression levels of IL-1β, IL-6, TNF-α, IκBα, p50 and p65 through regulating TLR4/MyD88 pathway to rehabilitate inflammation. In addition, dioscin markedly up-regulated the expression levels of SIRT1, HO-1, NQO1, GST and GCLM through increasing nuclear translocation of Nrf2 against oxidative stress. Furthermore, dioscin significantly decreased the expression levels of FasL, Fas, p53, Bak, Caspase-3/9, and upregulated Bcl-2 level through decreasing IRF9 level against apoptosis. In conclusion, dioscin showed protective effect against DMN-induced acute liver injury via ameliorating apoptosis, oxidative stress and inflammation, which should be developed as a new candidate for the treatment of acute liver injury in the future.
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dioscin induces apoptosis in human cervical carcinoma hela and siha cells through ros mediated dna damage and the mitochondrial signaling pathway
Molecules, 2016Co-Authors: Xinwei Zhao, Lina Xu, Yan Qi, Youwei Xu, Jinyong PengAbstract:Dioscin, a natural product, has activity against glioblastoma multiforme, lung cancer and colon cancer. In this study, the effects of dioscin against human cervical carcinoma HeLa and SiHa cells were further confirmed, and the possible mechanism(s) were investigated. A transmission electron microscopy (TEM) assay and DAPI staining were used to detect the cellular morphology. Flow cytometry was used to assay cell apoptosis, ROS and Ca2+ levels. Single cell gel electrophoresis and immunofluorescence assays were used to test DNA damage and cytochrome C release. The results showed that dioscin significantly inhibited cell proliferation and caused DNA damage in HeLa and SiHa cells. The mechanistic investigation showed that dioscin caused the release of cytochrome C from mitochondria into the cytosol. In addition, dioscin significantly up-regulated the protein levels of Bak, Bax, Bid, p53, caspase-3, caspase-9, and down-regulated the protein levels of Bcl-2 and Bcl-xl. Our work thus demonstrated that dioscin notably induces apoptosis in HeLa and SiHa cells through adjusting ROS-mediated DNA damage and the mitochondrial signaling pathway.
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in silico prediction of drug targets biological activities signal pathways and regulating networks of dioscin based on bioinformatics
BMC Complementary and Alternative Medicine, 2015Co-Authors: Lingli Zheng, Lina Xu, Yan Qi, Youwei Xu, Deshi Dong, Yanyan Zhao, Jinyong PengAbstract:Inverse docking technology has been a trend of drug discovery, and bioinformatics approaches have been used to predict target proteins, biological activities, signal pathways and molecular regulating networks affected by drugs for further pharmacodynamic and mechanism studies. In the present paper, inverse docking technology was applied to screen potential targets from potential drug target database (PDTD). Then, the corresponding gene information of the obtained drug-targets was applied to predict the related biological activities, signal pathways and processes networks of the compound by using MetaCore platform. After that, some most relevant regulating networks were considered, which included the nodes and relevant pathways of dioscin. 71 potential targets of dioscin from humans, 7 from rats and 8 from mice were screened, and the prediction results showed that the most likely targets of dioscin were cyclin A2, calmodulin, hemoglobin subunit beta, DNA topoisomerase I, DNA polymerase lambda, nitric oxide synthase and UDP-N-acetylhexosamine pyrophosphorylase, etc. Many diseases including experimental autoimmune encephalomyelitis of human, temporal lobe epilepsy of rat and ankylosing spondylitis of mouse, may be inhibited by dioscin through regulating immune response alternative complement pathway, G-protein signaling RhoB regulation pathway and immune response antiviral actions of interferons, etc. The most relevant networks (5 from human, 3 from rat and 5 from mouse) indicated that dioscin may be a TOP1 inhibitor, which can treat cancer though the cell cycle– transition and termination of DNA replication pathway. Dioscin can down regulate EGFR and EGF to inhibit cancer, and also has anti-inflammation activity by regulating JNK signaling pathway. The predictions of the possible targets, biological activities, signal pathways and relevant regulating networks of dioscin provide valuable information to guide further investigation of dioscin on pharmacodynamics and molecular mechanisms, which also suggests a practical and effective method for studies on the mechanism of other chemicals.
Yukimichi Kawada - One of the best experts on this subject based on the ideXlab platform.
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chemopreventive effects of Diosmin and hesperidin on n butyl n 4 hydroxybutyl nitrosamine induced urinary bladder carcinogenesis in male icr mice
International Journal of Cancer, 1997Co-Authors: Muzheng Yang, Takuji Tanaka, Hideki Mori, Yoshinobu Hirose, Takashi Deguchi, Yukimichi KawadaAbstract:The chemopreventive effects of 2 flavonoids (Diosmin and hesperidin) on N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN)-induced urinary-bladder carcinogenesis were examined in male ICR mice. Animals were divided into 11 groups, and groups 1 to 7 were given OH-BBN (500 ppm) in the drinking water for 6 weeks. Groups 2 to 4 were fed diets containing the test compounds (group 2, 1000 ppm Diosmin; group 3, 1000 ppm hesperidin; group 4,900 ppm Diosmin + 100 ppm hesperidin) for 8 weeks during the initiation phase, while groups 5 to 7 were fed these diets, respectively, for 24 weeks during the post-initiation phase. Groups 8 to 11 were controls, given only the test compounds or untreated basal diets throughout the experiment (weeks 1 to 32). The incidence of bladder lesions and cell-proliferation activity estimated by enumeration of silver-stained nucleolar-organizer-region-associated proteins (AgNORs) and by the 5-bromodeoxyuridine (BUdR)-labeling index was compared among the groups. Feeding of the test compounds, singly or in combination, during both phases caused a significant reduction in the frequency of bladder carcinoma and pre-neoplasia. Dietary administration of these compounds significantly decreased the AgNOR count and the BUdR-labeling index of various bladder lesions. These findings suggest that the flavonoids Diosmin and hesperidin, individually and in combination, are effective in inhibiting chemical carcinogenesis of the bladder, and that such inhibition might be partly related to suppression of cell proliferation. Int. J. Cancer 73:719–724, 1997. © 1997 Wiley-Liss, Inc.
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chemopreventive effects of Diosmin and hesperidin on n butyl n 4 hydroxybutyl nitrosamine induced urinary bladder carcinogenesis in male icr mice
International Journal of Cancer, 1997Co-Authors: Muzheng Yang, Takuji Tanaka, Hideki Mori, Yoshinobu Hirose, Takashi Deguchi, Yukimichi KawadaAbstract:The chemopreventive effects of 2 flavonoids (Diosmin and hesperidin) on N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN)-induced urinary-bladder carcinogenesis were examined in male ICR mice. Animals were divided into 11 groups, and groups 1 to 7 were given OH-BBN (500 ppm) in the drinking water for 6 weeks. Groups 2 to 4 were fed diets containing the test compounds (group 2, 1000 ppm Diosmin; group 3, 1000 ppm hesperidin; group 4,900 ppm Diosmin + 100 ppm hesperidin) for 8 weeks during the initiation phase, while groups 5 to 7 were fed these diets, respectively, for 24 weeks during the post-initiation phase. Groups 8 to 11 were controls, given only the test compounds or untreated basal diets throughout the experiment (weeks 1 to 32). The incidence of bladder lesions and cell-proliferation activity estimated by enumeration of silver-stained nucleolar-organizer-region-associated proteins (AgNORs) and by the 5-bromodeoxyuridine (BUdR)-labeling index was compared among the groups. Feeding of the test compounds, singly or in combination, during both phases caused a significant reduction in the frequency of bladder carcinoma and preneoplasia. Dietary administration of these compounds significantly decreased the AgNOR count and the BUdR-labeling index of various bladder lesions. These findings suggest that the flavonoids Diosmin and hesperidin, individually and in combination, are effective in inhibiting chemical carcinogenesis of the bladder, and that such inhibition might be partly related to suppression of cell proliferation.
Rabab Kamel - One of the best experts on this subject based on the ideXlab platform.
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Diosmin essential oil combination for dermal photo protection using a lipoid colloidal carrier
Journal of Photochemistry and Photobiology B-biology, 2017Co-Authors: Rabab Kamel, Haidy Abbas, Ahmed FayezAbstract:Abstract Solar irradiation induces skin inflammatory processes causing deleterious effects like premature ageing. In this study, the designed lipoid colloidal carrier (LCC) was loaded with Diosmin in combination with different essential oils, to be used as a topical photo-protective preparation. To investigate the ability of the essential oils to potentiate Diosmin effects, the Diosmin/essential oil-loaded LCCs (LCC2, LCC3 and LCC4) were compared to the Diosmin-loaded LCC (LCC1). The incorporated essential oils were those of Rosmarinus officinalis , Zingiber officinale or Vitis vinifera in LCC2, LCC3 and LCC4, respectively. All the LCCs had particle size (PS) values ranging from 121.1 to 144.3 nm with uniform distribution and, zeta potential (Z) values around 30 mV. Also, they all had high drug encapsulation efficiencies. LCC1 had the lowest anti-oxidant and in-vitro sun-blocking effect (p In-vivo photo-protective studies showed that all the formulated LCCs had a skin protective effect when compared to the positive control (p
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Diosmin essential oil combination for dermal photo protection using a lipoid colloidal carrier
Journal of Photochemistry and Photobiology B-biology, 2017Co-Authors: Rabab Kamel, Haidy Abbas, Ahmed M FayezAbstract:Solar irradiation induces skin inflammatory processes causing deleterious effects like premature ageing. In this study, the designed lipoid colloidal carrier (LCC) was loaded with Diosmin in combination with different essential oils, to be used as a topical photo-protective preparation. To investigate the ability of the essential oils to potentiate Diosmin effects, the Diosmin/essential oil-loaded LCCs (LCC2, LCC3 and LCC4) were compared to the Diosmin-loaded LCC (LCC1). The incorporated essential oils were those of Rosmarinus officinalis, Zingiber officinale or Vitis vinifera in LCC2, LCC3 and LCC4, respectively. All the LCCs had particle size (PS) values ranging from 121.1 to 144.3nm with uniform distribution and, zeta potential (Z) values around 30mV. Also, they all had high drug encapsulation efficiencies. LCC1 had the lowest anti-oxidant and in-vitro sun-blocking effect (p<0.05). In-vivo photo-protective studies showed that all the formulated LCCs had a skin protective effect when compared to the positive control (p<0.05); however LCC1 had the lowest anti-erythemal and anti-wrinkling effect. Histological studies proved the efficacy of the designed LCCs as skin anti-photoageing, with LCC1 showing the lowest anti-inflammatory and anti-wrinkling effect, while LCC2 had the highest anti-wrinkling effect. These results indicated that the suggested Diosmin/essential oil combinations improved the anti-oxidant, sun-blocking and anti-photoageing effects of Diosmin. After one year of storage, the LCCs showed satisfactory physical stability. This study presents the designed LCCs as safe and effective nano-structured dermal care products containing 'all-natural' components.
Takuji Tanaka - One of the best experts on this subject based on the ideXlab platform.
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chemopreventive effects of Diosmin and hesperidin on n butyl n 4 hydroxybutyl nitrosamine induced urinary bladder carcinogenesis in male icr mice
International Journal of Cancer, 1997Co-Authors: Muzheng Yang, Takuji Tanaka, Hideki Mori, Yoshinobu Hirose, Takashi Deguchi, Yukimichi KawadaAbstract:The chemopreventive effects of 2 flavonoids (Diosmin and hesperidin) on N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN)-induced urinary-bladder carcinogenesis were examined in male ICR mice. Animals were divided into 11 groups, and groups 1 to 7 were given OH-BBN (500 ppm) in the drinking water for 6 weeks. Groups 2 to 4 were fed diets containing the test compounds (group 2, 1000 ppm Diosmin; group 3, 1000 ppm hesperidin; group 4,900 ppm Diosmin + 100 ppm hesperidin) for 8 weeks during the initiation phase, while groups 5 to 7 were fed these diets, respectively, for 24 weeks during the post-initiation phase. Groups 8 to 11 were controls, given only the test compounds or untreated basal diets throughout the experiment (weeks 1 to 32). The incidence of bladder lesions and cell-proliferation activity estimated by enumeration of silver-stained nucleolar-organizer-region-associated proteins (AgNORs) and by the 5-bromodeoxyuridine (BUdR)-labeling index was compared among the groups. Feeding of the test compounds, singly or in combination, during both phases caused a significant reduction in the frequency of bladder carcinoma and pre-neoplasia. Dietary administration of these compounds significantly decreased the AgNOR count and the BUdR-labeling index of various bladder lesions. These findings suggest that the flavonoids Diosmin and hesperidin, individually and in combination, are effective in inhibiting chemical carcinogenesis of the bladder, and that such inhibition might be partly related to suppression of cell proliferation. Int. J. Cancer 73:719–724, 1997. © 1997 Wiley-Liss, Inc.
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chemopreventive effects of Diosmin and hesperidin on n butyl n 4 hydroxybutyl nitrosamine induced urinary bladder carcinogenesis in male icr mice
International Journal of Cancer, 1997Co-Authors: Muzheng Yang, Takuji Tanaka, Hideki Mori, Yoshinobu Hirose, Takashi Deguchi, Yukimichi KawadaAbstract:The chemopreventive effects of 2 flavonoids (Diosmin and hesperidin) on N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN)-induced urinary-bladder carcinogenesis were examined in male ICR mice. Animals were divided into 11 groups, and groups 1 to 7 were given OH-BBN (500 ppm) in the drinking water for 6 weeks. Groups 2 to 4 were fed diets containing the test compounds (group 2, 1000 ppm Diosmin; group 3, 1000 ppm hesperidin; group 4,900 ppm Diosmin + 100 ppm hesperidin) for 8 weeks during the initiation phase, while groups 5 to 7 were fed these diets, respectively, for 24 weeks during the post-initiation phase. Groups 8 to 11 were controls, given only the test compounds or untreated basal diets throughout the experiment (weeks 1 to 32). The incidence of bladder lesions and cell-proliferation activity estimated by enumeration of silver-stained nucleolar-organizer-region-associated proteins (AgNORs) and by the 5-bromodeoxyuridine (BUdR)-labeling index was compared among the groups. Feeding of the test compounds, singly or in combination, during both phases caused a significant reduction in the frequency of bladder carcinoma and preneoplasia. Dietary administration of these compounds significantly decreased the AgNOR count and the BUdR-labeling index of various bladder lesions. These findings suggest that the flavonoids Diosmin and hesperidin, individually and in combination, are effective in inhibiting chemical carcinogenesis of the bladder, and that such inhibition might be partly related to suppression of cell proliferation.
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chemoprevention of azoxymethane induced rat colon carcinogenesis by the naturally occurring flavonoids Diosmin and hesperidin
Carcinogenesis, 1997Co-Authors: Takuji Tanaka, Hideki Mori, Hiroki Makita, Kunihiro Kawabata, Mikio Kakumoto, Kumiko Satoh, Akira Hara, T Sumida, H OgawaAbstract:: The modulating effects of dietary feeding of two flavonoids, Diosmin and hesperidin, both alone and in combination, during the initiation and post-initiation phases on colon carcinogenesis initiated with azoxymethane (AOM), were investigated in male F344 rats. Animals were initiated with AOM by weekly s.c. injections of 15 mg/kg body wt for 3 weeks to induced colon neoplasms. Rats were fed the diets containing Diosmin (1000 ppm), hesperidin (1000 ppm) or Diosmin (900 ppm) + hesperidin (100 ppm) for 5 weeks (initiation treatment) or 28 weeks (post-initiation treatment). The others contained the groups of rats treated with Diosmin, hesperidin alone or in combination, and untreated. At the end of the study (32 weeks), the incidence and multiplicity of neoplasms (adenoma and adenocarcinoma) in the large intestine of rats initiated with AOM together with, or followed by, a diet containing Diosmin or hesperidin were significantly smaller than those of rats given AOM alone (P <0.001). The combination regimen during the initiation and post-initiation stages also inhibited the development of colonic neoplasms, but the tumor data did not indicate any beneficial effect of Diosmin and hesperidin administered together as compared with when these agents were given individually. In addition, feeding of Diosmin and hesperidin, both alone and in combination, significantly inhibited the development of aberrant crypt foci. As for cell proliferation biomarkers, dietary exposure of Diosmin and hesperidin significantly decreased the 5'-bromodeoxyuridine-labeling index and argyrophilic nuclear organizer region's number in crypt cells, colonic mucosal ornithine decarboxylase activity, and polyamine levels in the blood. These results indicate that Diosmin and hesperidin, both alone and in combination, act as a chemopreventive agent against colon carcinogenesis, and such effects may be partly due to suppression of cell proliferation in the colonic crypts, although precise mechanisms should be clarified.
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modulation of n methyl n amylnitrosamine induced rat oesophageal tumourigenesis by dietary feeding of Diosmin and hesperidin both alone and in combination
Carcinogenesis, 1997Co-Authors: Takuji Tanaka, Hideki Mori, Hiroki Makita, Kunihiro Kawabata, Mikio Kakumoto, Kumiko Satoh, Akira Hara, T Sumida, K Fukutani, H OgawaAbstract:The modifying effects of flavonoids Diosmin and hesperidin during the initiation and post-initiation phases of oesophageal carcinogenesis initiated with N-methyl-N-amylnitrosamine (MNAN) were investigated in male Wistar rats. At 7 weeks of age, all animals except those treated each test chemical alone and control groups were given weekly intraperitoneal injections of MNAN (12.5 mg/kg body weight/injection) for 12 weeks to induce oesophageal neoplasms. For examining the modifying effects of 'initiation' treatment of test compounds, groups of animals were fed the diets containing 1000 ppm Diosmin and 1000 ppm hesperidin, and the diet containing both compounds (900 ppm Diosmin and 100 ppm hesperidin) for 13 weeks, starting 7 days before the MNAN dosing and then switched to the basal diet. For examining the modifying effects of 'post-initiation' treatment of these compounds, the groups given MNAN and a basal diet were switched to the experimental diets containing Diosmin, hesperidin or Diosmin combined with hesperidin at 1 week after the stop of MNAN injection, and maintained on these diets for 7 weeks. The other groups consisted of rats given test compounds alone or untreated rats. All animals were necropsied at the termination of the study (week 20) to determine the incidences of oesophageal neoplasms and preneoplasms, blood polyamine levels, and cell proliferation activity estimated by 5-bromodeoxyuridine (BrdU)-labelling index and by morphometric analysis of silver-stained nucleolar organizer regions' protein (AgNORs). A number of oesophageal neoplasms developed in rats treated with MNAN alone (75% and 100% incidences of carcinoma and papilloma, respectively). 'Initiation' feeding of Diosmin significantly decreased the incidence of squamous cell carcinoma (P < 0.05). Also, 'initiation feeding' of both compounds singly or in combination caused a significant reduction in the multiplicities of oesophageal carcinoma and papilloma (Diosmin, 78 and 58% reduction; hesperidin, 70 and 50% reduction; and the combination regimen, 70 and 30% reduction, P < 0.005). 'Post-initiation' feeding slightly decreased the multiplicities of these oesophageal neoplasms. Also, these dietary regimens reduced the multiplicities of preneoplastic lesions (hyperplasia and severe dysplasia; P < 0.05). There were no pathological alterations in rats treated with both compounds alone or the combined regimen alone or those in an untreated control group. Similarly, feeding of these compounds significantly decreased the expression of cell proliferation biomarkers (BrdU-labelling index and AgNORs number) of the non-lesional oesophageal epithelium (P < 0.05). Blood polyamine concentrations were also lowered in rats given the carcinogen and test compounds, both alone and in combination, when compared with those of rats given MNAN alone (P < 0.05). These findings suggest that Diosmin and hesperidin supplementation, individually or in combination, is effective in inhibiting the development of oesophageal cancer induced by MNAN when given during the initiation phase, and such inhibition might be related to suppression of increased cell proliferation caused by MNAN in the oesophageal mucosa.
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chemoprevention of 4 nitroquinoline 1 oxide induced oral carcinogenesis in rats by flavonoids Diosmin and hesperidin each alone and in combination
Cancer Research, 1997Co-Authors: Takuji Tanaka, Hideki Mori, Hiroki Makita, Kumiko Satoh, Akira Hara, T Sumida, Masami Ohnishi, K Fukutani, H OgawaAbstract:The modifying effects of the two flavonoids Diosmin and hesperidin given during the initiation and postinitiation phases of oral carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. The compounds were tested alone and in combination. At 6 weeks of age, animals were divided into experimental and control groups and fed diets containing 1000 ppm Diosmin and 1000 ppm hesperidin and a diet containing both compounds (900 ppm Diosmin and 100 ppm hesperidin). At 7 weeks of age, all animals except those treated with each test chemical alone and control groups were given 4-NQO (20 ppm) in the drinking water for 8 weeks to induce oral cancer. Starting 7 days before the 4-NQO exposure, groups of animals were fed the diets containing test chemicals for 10 weeks and then switched to the basal diet. Starting 1 week after the cessation of 4-NQO exposure, the groups given 4-NQO and a basal diet were switched to the diets containing Diosmin, hesperidin, or Diosmin combined with hesperidin and maintained on these diets for 22 weeks. The other groups consisted of rats given Diosmin (1000 ppm), hesperidin (1000 ppm), and the combination regimen of these two compounds (900 ppm Diosmin with 100 ppm hesperidin) alone, and untreated rats. All animals were necropsied at the termination of the study (week 32). The incidences of tongue lesions (neoplasms and preneoplasms), polyamine levels in the tongue tissue, and cell proliferation activity estimated by a 5-bromodeoxyuridine-labeling index and by morphometric analysis of silver-stained nucleolar organizer regions protein were compared among the groups. Feeding of both compounds singly or in combination during the initiation phase caused a significant reduction in the frequency of tongue carcinoma [Diosmin, 68% reduction (P < 0.01); hesperidin, 75% reduction (P < 0.005); and the combination regimen, 69% (P < 0.05)]. When fed the test compounds singly or the combination regimen after 4-NQO exposure, the frequency of tongue cancer was also decreased [Diosmin, 77% reduction (P < 0.005); hesperidin, 62% reduction (P < 0.05); and the combination regimen, 77% (P < 0.005)]. The incidences of oral preneoplasia (hyperplasia and dysplasia) in these groups were also decreased when compared with carcinogen controls (P < 0.05-P < 0.001). There were no pathological alterations in rats treated with test compounds or the combined regimen alone or those in an untreated control group. Dietary administration of these compounds significantly decreased the expression of cell proliferation biomarkers (5-bromodeoxyuridine-labeling index and silver-stained nucleolar organizer regions protein number) of the nonlesional tongue squamous epithelium (P < 0.05). Also, polyamine concentrations in the oral mucosa were lowered in rats given the carcinogen and test compounds, alone and in combination, compared with those of rats given 4-NQO alone (P < 0.05). These findings suggest that supplementation with the flavonoids Diosmin and hesperidin, individually and in combination, is effective in inhibiting the development of oral neoplasms induced by 4-NQO, and such inhibition might be related to suppression of increased cell proliferation caused by 4-NQO in the oral mucosa.
Hideki Mori - One of the best experts on this subject based on the ideXlab platform.
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chemopreventive effects of Diosmin and hesperidin on n butyl n 4 hydroxybutyl nitrosamine induced urinary bladder carcinogenesis in male icr mice
International Journal of Cancer, 1997Co-Authors: Muzheng Yang, Takuji Tanaka, Hideki Mori, Yoshinobu Hirose, Takashi Deguchi, Yukimichi KawadaAbstract:The chemopreventive effects of 2 flavonoids (Diosmin and hesperidin) on N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN)-induced urinary-bladder carcinogenesis were examined in male ICR mice. Animals were divided into 11 groups, and groups 1 to 7 were given OH-BBN (500 ppm) in the drinking water for 6 weeks. Groups 2 to 4 were fed diets containing the test compounds (group 2, 1000 ppm Diosmin; group 3, 1000 ppm hesperidin; group 4,900 ppm Diosmin + 100 ppm hesperidin) for 8 weeks during the initiation phase, while groups 5 to 7 were fed these diets, respectively, for 24 weeks during the post-initiation phase. Groups 8 to 11 were controls, given only the test compounds or untreated basal diets throughout the experiment (weeks 1 to 32). The incidence of bladder lesions and cell-proliferation activity estimated by enumeration of silver-stained nucleolar-organizer-region-associated proteins (AgNORs) and by the 5-bromodeoxyuridine (BUdR)-labeling index was compared among the groups. Feeding of the test compounds, singly or in combination, during both phases caused a significant reduction in the frequency of bladder carcinoma and pre-neoplasia. Dietary administration of these compounds significantly decreased the AgNOR count and the BUdR-labeling index of various bladder lesions. These findings suggest that the flavonoids Diosmin and hesperidin, individually and in combination, are effective in inhibiting chemical carcinogenesis of the bladder, and that such inhibition might be partly related to suppression of cell proliferation. Int. J. Cancer 73:719–724, 1997. © 1997 Wiley-Liss, Inc.
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chemopreventive effects of Diosmin and hesperidin on n butyl n 4 hydroxybutyl nitrosamine induced urinary bladder carcinogenesis in male icr mice
International Journal of Cancer, 1997Co-Authors: Muzheng Yang, Takuji Tanaka, Hideki Mori, Yoshinobu Hirose, Takashi Deguchi, Yukimichi KawadaAbstract:The chemopreventive effects of 2 flavonoids (Diosmin and hesperidin) on N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN)-induced urinary-bladder carcinogenesis were examined in male ICR mice. Animals were divided into 11 groups, and groups 1 to 7 were given OH-BBN (500 ppm) in the drinking water for 6 weeks. Groups 2 to 4 were fed diets containing the test compounds (group 2, 1000 ppm Diosmin; group 3, 1000 ppm hesperidin; group 4,900 ppm Diosmin + 100 ppm hesperidin) for 8 weeks during the initiation phase, while groups 5 to 7 were fed these diets, respectively, for 24 weeks during the post-initiation phase. Groups 8 to 11 were controls, given only the test compounds or untreated basal diets throughout the experiment (weeks 1 to 32). The incidence of bladder lesions and cell-proliferation activity estimated by enumeration of silver-stained nucleolar-organizer-region-associated proteins (AgNORs) and by the 5-bromodeoxyuridine (BUdR)-labeling index was compared among the groups. Feeding of the test compounds, singly or in combination, during both phases caused a significant reduction in the frequency of bladder carcinoma and preneoplasia. Dietary administration of these compounds significantly decreased the AgNOR count and the BUdR-labeling index of various bladder lesions. These findings suggest that the flavonoids Diosmin and hesperidin, individually and in combination, are effective in inhibiting chemical carcinogenesis of the bladder, and that such inhibition might be partly related to suppression of cell proliferation.
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chemoprevention of azoxymethane induced rat colon carcinogenesis by the naturally occurring flavonoids Diosmin and hesperidin
Carcinogenesis, 1997Co-Authors: Takuji Tanaka, Hideki Mori, Hiroki Makita, Kunihiro Kawabata, Mikio Kakumoto, Kumiko Satoh, Akira Hara, T Sumida, H OgawaAbstract:: The modulating effects of dietary feeding of two flavonoids, Diosmin and hesperidin, both alone and in combination, during the initiation and post-initiation phases on colon carcinogenesis initiated with azoxymethane (AOM), were investigated in male F344 rats. Animals were initiated with AOM by weekly s.c. injections of 15 mg/kg body wt for 3 weeks to induced colon neoplasms. Rats were fed the diets containing Diosmin (1000 ppm), hesperidin (1000 ppm) or Diosmin (900 ppm) + hesperidin (100 ppm) for 5 weeks (initiation treatment) or 28 weeks (post-initiation treatment). The others contained the groups of rats treated with Diosmin, hesperidin alone or in combination, and untreated. At the end of the study (32 weeks), the incidence and multiplicity of neoplasms (adenoma and adenocarcinoma) in the large intestine of rats initiated with AOM together with, or followed by, a diet containing Diosmin or hesperidin were significantly smaller than those of rats given AOM alone (P <0.001). The combination regimen during the initiation and post-initiation stages also inhibited the development of colonic neoplasms, but the tumor data did not indicate any beneficial effect of Diosmin and hesperidin administered together as compared with when these agents were given individually. In addition, feeding of Diosmin and hesperidin, both alone and in combination, significantly inhibited the development of aberrant crypt foci. As for cell proliferation biomarkers, dietary exposure of Diosmin and hesperidin significantly decreased the 5'-bromodeoxyuridine-labeling index and argyrophilic nuclear organizer region's number in crypt cells, colonic mucosal ornithine decarboxylase activity, and polyamine levels in the blood. These results indicate that Diosmin and hesperidin, both alone and in combination, act as a chemopreventive agent against colon carcinogenesis, and such effects may be partly due to suppression of cell proliferation in the colonic crypts, although precise mechanisms should be clarified.
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modulation of n methyl n amylnitrosamine induced rat oesophageal tumourigenesis by dietary feeding of Diosmin and hesperidin both alone and in combination
Carcinogenesis, 1997Co-Authors: Takuji Tanaka, Hideki Mori, Hiroki Makita, Kunihiro Kawabata, Mikio Kakumoto, Kumiko Satoh, Akira Hara, T Sumida, K Fukutani, H OgawaAbstract:The modifying effects of flavonoids Diosmin and hesperidin during the initiation and post-initiation phases of oesophageal carcinogenesis initiated with N-methyl-N-amylnitrosamine (MNAN) were investigated in male Wistar rats. At 7 weeks of age, all animals except those treated each test chemical alone and control groups were given weekly intraperitoneal injections of MNAN (12.5 mg/kg body weight/injection) for 12 weeks to induce oesophageal neoplasms. For examining the modifying effects of 'initiation' treatment of test compounds, groups of animals were fed the diets containing 1000 ppm Diosmin and 1000 ppm hesperidin, and the diet containing both compounds (900 ppm Diosmin and 100 ppm hesperidin) for 13 weeks, starting 7 days before the MNAN dosing and then switched to the basal diet. For examining the modifying effects of 'post-initiation' treatment of these compounds, the groups given MNAN and a basal diet were switched to the experimental diets containing Diosmin, hesperidin or Diosmin combined with hesperidin at 1 week after the stop of MNAN injection, and maintained on these diets for 7 weeks. The other groups consisted of rats given test compounds alone or untreated rats. All animals were necropsied at the termination of the study (week 20) to determine the incidences of oesophageal neoplasms and preneoplasms, blood polyamine levels, and cell proliferation activity estimated by 5-bromodeoxyuridine (BrdU)-labelling index and by morphometric analysis of silver-stained nucleolar organizer regions' protein (AgNORs). A number of oesophageal neoplasms developed in rats treated with MNAN alone (75% and 100% incidences of carcinoma and papilloma, respectively). 'Initiation' feeding of Diosmin significantly decreased the incidence of squamous cell carcinoma (P < 0.05). Also, 'initiation feeding' of both compounds singly or in combination caused a significant reduction in the multiplicities of oesophageal carcinoma and papilloma (Diosmin, 78 and 58% reduction; hesperidin, 70 and 50% reduction; and the combination regimen, 70 and 30% reduction, P < 0.005). 'Post-initiation' feeding slightly decreased the multiplicities of these oesophageal neoplasms. Also, these dietary regimens reduced the multiplicities of preneoplastic lesions (hyperplasia and severe dysplasia; P < 0.05). There were no pathological alterations in rats treated with both compounds alone or the combined regimen alone or those in an untreated control group. Similarly, feeding of these compounds significantly decreased the expression of cell proliferation biomarkers (BrdU-labelling index and AgNORs number) of the non-lesional oesophageal epithelium (P < 0.05). Blood polyamine concentrations were also lowered in rats given the carcinogen and test compounds, both alone and in combination, when compared with those of rats given MNAN alone (P < 0.05). These findings suggest that Diosmin and hesperidin supplementation, individually or in combination, is effective in inhibiting the development of oesophageal cancer induced by MNAN when given during the initiation phase, and such inhibition might be related to suppression of increased cell proliferation caused by MNAN in the oesophageal mucosa.
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chemoprevention of 4 nitroquinoline 1 oxide induced oral carcinogenesis in rats by flavonoids Diosmin and hesperidin each alone and in combination
Cancer Research, 1997Co-Authors: Takuji Tanaka, Hideki Mori, Hiroki Makita, Kumiko Satoh, Akira Hara, T Sumida, Masami Ohnishi, K Fukutani, H OgawaAbstract:The modifying effects of the two flavonoids Diosmin and hesperidin given during the initiation and postinitiation phases of oral carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. The compounds were tested alone and in combination. At 6 weeks of age, animals were divided into experimental and control groups and fed diets containing 1000 ppm Diosmin and 1000 ppm hesperidin and a diet containing both compounds (900 ppm Diosmin and 100 ppm hesperidin). At 7 weeks of age, all animals except those treated with each test chemical alone and control groups were given 4-NQO (20 ppm) in the drinking water for 8 weeks to induce oral cancer. Starting 7 days before the 4-NQO exposure, groups of animals were fed the diets containing test chemicals for 10 weeks and then switched to the basal diet. Starting 1 week after the cessation of 4-NQO exposure, the groups given 4-NQO and a basal diet were switched to the diets containing Diosmin, hesperidin, or Diosmin combined with hesperidin and maintained on these diets for 22 weeks. The other groups consisted of rats given Diosmin (1000 ppm), hesperidin (1000 ppm), and the combination regimen of these two compounds (900 ppm Diosmin with 100 ppm hesperidin) alone, and untreated rats. All animals were necropsied at the termination of the study (week 32). The incidences of tongue lesions (neoplasms and preneoplasms), polyamine levels in the tongue tissue, and cell proliferation activity estimated by a 5-bromodeoxyuridine-labeling index and by morphometric analysis of silver-stained nucleolar organizer regions protein were compared among the groups. Feeding of both compounds singly or in combination during the initiation phase caused a significant reduction in the frequency of tongue carcinoma [Diosmin, 68% reduction (P < 0.01); hesperidin, 75% reduction (P < 0.005); and the combination regimen, 69% (P < 0.05)]. When fed the test compounds singly or the combination regimen after 4-NQO exposure, the frequency of tongue cancer was also decreased [Diosmin, 77% reduction (P < 0.005); hesperidin, 62% reduction (P < 0.05); and the combination regimen, 77% (P < 0.005)]. The incidences of oral preneoplasia (hyperplasia and dysplasia) in these groups were also decreased when compared with carcinogen controls (P < 0.05-P < 0.001). There were no pathological alterations in rats treated with test compounds or the combined regimen alone or those in an untreated control group. Dietary administration of these compounds significantly decreased the expression of cell proliferation biomarkers (5-bromodeoxyuridine-labeling index and silver-stained nucleolar organizer regions protein number) of the nonlesional tongue squamous epithelium (P < 0.05). Also, polyamine concentrations in the oral mucosa were lowered in rats given the carcinogen and test compounds, alone and in combination, compared with those of rats given 4-NQO alone (P < 0.05). These findings suggest that supplementation with the flavonoids Diosmin and hesperidin, individually and in combination, is effective in inhibiting the development of oral neoplasms induced by 4-NQO, and such inhibition might be related to suppression of increased cell proliferation caused by 4-NQO in the oral mucosa.