Protective effect of Pai-Nong-San against AOM/DSS-induced CAC in mice through inhibiting the Wnt signaling pathway / 中国天然药物

Pai-Nong-San (PNS), a prescription of traditional Chinese medicine, has been used for years to treat abscessation-induced diseases including colitis and colorectal cancer. This study was aimed to investigate the preventive effects and possible protective mechanism of PNS on a colitis-associated colorectal cancer (CAC) mouse model induced by azoxymethane (AOM)/dextran sodium sulfate (DSS). The macroscopic and histopathologic examinations of colon injury and DAI score were observed. The inflammatory indicators of intestinal immunity were determined by immunohistochemistry and immunofluorescence. The high throughput 16S rRNA sequence of gut microbiota in the feces of mice was performed. Western blot was used to investigate the protein expression of the Wnt signaling pathway in colon tissues. PNS improved colon injury, as manifested by the alleviation of hematochezia, decreased DAI score, increased colon length, and reversal of pathological changes. PNS treatment protected against AOM/DSS-induced colon inflammation by regulating the expression of CD4

Effect of a hyperlipidic diet rich in omegas 3, 6 and 9 on aberrant crypt formation in rat colonic mucosa / Efeito de uma dieta hiperlipídica rica em ômegas 3, 6 e 9 na formação de criptas aberrantes em mucosa cólica de ratos

PURPOSE: To determine whether a hypercaloric and hyperlipidic diet enriched with polyunsaturated fatty acids influences the formation of aberrant crypt foci (ACF) in colonic mucosa of Wistar rats treated with azoxymethane (AOM). METHODS: At eight weeks of life, the rats were assigned to four groups: Group I―standard diet (STD) not treated with AOM; Group II―hypercaloric and hyperlipidic diet (FED), not treated with AOM; Group III―STD, treated with AOM; Group IV―FED, treated with AOM. At 16 weeks, the animals were injected intraperitoneal with 0.9 percent saline solution (Group I and II) or AOM at 15mg/Kg (Groups III and IV) once a week for two weeks. Fifteen weeks later, the animals were euthanized. RESULTS: FED promoted weight gain in Groups II and IV compared to Groups I and III, respectively. The groups did not differ with regard to the total number of ACF. The Chi-square test revealed no predominance of the presence of foci with <4 crypts. However, foci with ≥5 crypts were proportionally more prevalent in Group III than in Group IV (p=0.043). CONCLUSION: The administration of polyunsaturated fatty acids did not interfere with the formation of aberrant crypt foci, but reduced ACF multiplicity, exercising an attenuating effect on carcinogenesis.

OBJETIVO: Determinar se uma dieta hipercalórica, hiperlipídica, rica em ácidos graxos poliinsaturados (FED) tem influência na formação de focos de cripta aberrante (FCA) em mucosa cólica de ratos Wistar expostos ao azoximetano (AOM). MÉTODOS: Com oito semanas de vida, os ratos foram distribuídos em quatro grupos: Grupo I: Dieta padrão (SD) sem AOM; Grupo II: FED, sem AOM; Grupo III: SD, com AOM; Grupo IV: FED com AOM. Com 16 semanas, os animais dos grupos I e II receberam injeções intraperitoneais de solução salina 0,9 por cento, enquanto os dos grupos III e IV receberam AOM na dose de 15mg/Kg de peso, 1 vez por semana por duas semanas. Quinze semanas após, os animais foram mortos. RESULTADOS: FED promoveu aumento de peso nos grupos II e IV em relação aos grupos I e III. Não houve aumento significante no número total de FCA entre os grupos. Em relação à multiplicidade das criptas por FCA, o teste do qui-quadrado mostrou que não houve predominância da presença <4 criptas por foco. Contudo, focos ≥5 criptas foram proporcionalmente mais prevalentes no grupo III que no grupo IV (p=0,043). CONCLUSÃO: Os ácidos graxos poliinsaturados não interferem na formação de focos de cripta aberrante, contudo reduz sua multiplicidade, exercendo efeito atenuador na carcinogênese.

Inhibition of lipid peroxidation and enhancement of GST activity by cardamom and cinnamon during chemically induced colon carcinogenesis in Swiss albino mice.

Globally, colorectal cancer is the third commonest cancer in men since 1975.The present study focuses on the preventive strategies aimed at reducing the incidences and mortality of large bowel cancer. Chemoprevention of colon cancer appears to be a very realistic possibility because various intermediate stages have been identified preceding the development of malignant colonic tumors. Several studies have demonstrated that generous consumption of vegetables reduces the risk of colon cancer. This idea has prompted the present investigation to search for some novel plant products, which may have possible anticarcinogenic activity. It has already been proved from various experiments that chemopreventive agents, by virtue of their anti-oxidant, anti-inflammatory, anti-proliferative, apoptosis-inducing activity, act at various levels including molecular, cellular, tissue and organ levels to interfere with carcinogens. Previous studies from our laboratory have already reported the inhibitory effect of cinnamon and cardamom on azoxymethane induced colon carcinogenesis by virtue of their anti-inflammatory, anti-proliferative and pro-apoptotic activity. This particular experiment was carried out to assess the anti-oxidative potential of these spices. Aqueous suspensions of cinnamon and cardamom have been shown to enhance the level of detoxifying enzyme (GST activity) with simultaneous decrease in lipid peroxidation levels in the treatment groups when compared to that of the carcinogen control group.

Preventive effects of a flavonoid myricitrin on the formation of azoxymethane-induced premalignant lesions in colons of rats.

The preventive effect of dietary exposure to a flavonoid myricitrin of azoxymethane (AOM)-induced aberrant crypt foci (ACF) and beta-catenin-accumulated crypts (BCAC) formation was investigated in male F344 rats. Thirty-four rats were divided randomly into five experimental groups. Rats in groups 1-3 were given subcutaneous injections of AOM (15 mg/kg body weight) once a week for 3 weeks. Starting 1 week before the first injection of AOM, rats in groups 2 and 3 were fed a diet containing 500 or 1000 ppm myricitrin, respectively, for 11 weeks. Rats in group 4 were fed a diet containing 1000 ppm myricitrin. Rats in groups 1 and 5 were given the basal diet alone during the study. The experiment was terminated 11 weeks after the start. The frequency of ACF per colon in group 3 treated with AOM and 1000 ppm myricitrin was significantly lower than that in group 1 treated with AOM alone (p<0.01). Furthermore, dietary myricitrin at both doses (groups 2 and 3) significantly inhibited the formation of BCAC when compared to group 1 (p<0.05). These results indicate that myricitrin had possible chemopreventive effects in the present short-term colon carcinogenesis bioassays and suggest that longer exposure may cause suppression of tumor development.

Study of superoxide dismutase's expression in the colon produced by azoxymethane and inositol hexaphosfate's paper, in mice

PURPOSE: To investigate the expression of superoxide dismutase (SOD), with use of antioxidant inositol hexaphosfate, in the presence of the carcinogen azoxymethane, in FCA of colon rats. METHODS: Wistar rats (n=48) were distributed in four groups of 12 mice. Divided in control (n=12); with azoxymethane administration AOM (n=12); administration of IP6 (n=12) and with administration of IP6/AOM (n=12). The subcutaneous administration of azoxymethane happened in the week 3 and 4 of the experiment, in dose 20mg/Kg, weekly; and administration of IP6 to 1 percent in water of drinking for 6 weeks in the group 3 and 4. The identification of the expression SOD-1 was accomplished through the quantification imunohistochemistry by the image processing attended by computer in crypts and focus of aberrant crypts in right colon. RESULTS: The group control presented expression of SOD1, on average 16,0 percent; group AOM, 26,7 percent; group IP6, 16,9 percent; group IP6/AOM, 20,9 percent. Variance analysis among the groups, was calculated 0,0078. CONCLUSION: The azoxymethane increase expression SOD1, while inositol hexaphosphate decreases in a significant way the expression of SOD1 promoted by the administration of the carcinogen azoxymethane.

OBJETIVO: Investigar a expressão de superóxido dismutase, com uso de antioxidante inositol hexafosfato, na presença do carcinógeno azoximetano em FCA de cólon de ratos. MÉTODOS: Quarenta e oito ratos Wistar, distribuídos em 4 grupos, divididos em controle (n=12); com administração de azoximetano AOM (n=12); administração de IP6 (n=12) e com administração de IP6/AOM (n=12). A administração subcutânea de azoximetano aconteceu na semana 3 e 4 do experimento, em dose 20mg/Kg, semanal; e administração de IP6 a 1 por cento em água de beber durante 6 semanas no grupo 3 e 4. A identificação da expressão SOD1 foi realizada através da quantificação imunohistoquimíca pelo processamento de imagem assistida por computador em criptas e focos de cripta aberrante em cólon direito. RESULTADOS: O grupo controle apresentou expressão de SOD1, em média 16,0 por cento; grupo AOM, 26,7 por cento; grupo IP6, 16,9 por cento; grupo IP6/AOM, 20,9 por cento. Análise de variância entre os grupos calculou-se 0,0078. CONCLUSÃO: A expressão de SOD-1 mostrou aumento significativo na presença de azoximetano e quando administrou-se IP6 concomitante houve diminuição na expressão de SOD1 promovido pela administração do carcinógeno azoximetano.

Dietary cardamom inhibits the formation of azoxymethane-induced aberrant crypt foci in mice and reduces COX-2 and iNOS expression in the colon.

Recently, considerable attention has been focused on identifying naturally occurring chemopreventive compounds capable of inhibiting, retarding, or reversing the multi-step carcinogenesis. The primary aim of the present study was to identify the effects of a commonly consumed spice, viz., cardamom against azoxymethane (AOM) induced colonic aberrant crypt foci (ACF) in Swiss Albino mice. The secondary aim, was to explore the ability of cardamom to modulate the status of proliferation and apoptosis, and to understand its role in altering cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Male Swiss albino mice were injected with AOM (dose: 5mg/Kg body weight) or saline (Group 1) weekly once for two weeks. The AOM-injected mice were randomly assigned to two groups (Groups 2 and 3). While all the groups were on standard lab chow, Group 3 received oral doses of 0.5% cardamom, in aqueous suspension, daily for 8 weeks. Following treatment, significant reduction in the incidences of aberrant crypt foci (p<0.05) was observed. This reduction in ACF was accompanied by suppression of cell proliferation (mean Brdu LI in carcinogen control =13.91+/-3.31, and 0.5% cardamom =2.723+/-0.830) and induction of apoptosis (mean AI in carcinogen control=1.547+/-0.42 and 0.5% cardamom = 6.61+/-0.55). Moreover, reduction of both COX-2 and iNOS expression was also observed. These results suggest that aqueous suspensions of cardamom have protective effects on experimentally induced colon carcinogenesis. Cardamom as a whole and its active components require further attention if the use of this spice is to be recommended for cancer prevention.