Pre-Administration of Berberine Exerts Chemopreventive Effects in AOM/DSS-Induced Colitis-Associated Carcinogenesis Mice via Modulating Inflammation and Intestinal Microbiota
Inflammatory activation and intestinal flora imbalance play an essential role in the development and progression of colorectal cancer (CRC). Berberine (BBR) has attracted great attention in recent years due to its heath-related benefits in inflammatory disorders and tumors, but the intricate mechani...
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| Veröffentlicht in: | Nutrients 2022-02, Vol.14 (4), p.726 |
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| creator | Deng, Jiaqiang Zhao, Lili Yuan, Xieyong Li, Yan Shi, Junyang Zhang, Hua Zhao, Yuxuan Han, Liping Wang, Huani Yan, Yan Zhao, Hong Wang, Haojie Zou, Fangdong |
| description | Inflammatory activation and intestinal flora imbalance play an essential role in the development and progression of colorectal cancer (CRC). Berberine (BBR) has attracted great attention in recent years due to its heath-related benefits in inflammatory disorders and tumors, but the intricate mechanisms have not been fully elucidated. In this study, the effects and the mechanism of BBR on colon cancer were investigated in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated carcinogenesis mice model. Our results showed that pre-administration of BBR showed a decrease in weight loss, disease activity index (DAI) score, and the number of colon tumors in mice, compared with the model group. The evidence from pathological examination indicated that the malignancy of intestinal tumors was ameliorated after pre-administration of BBR. Additionally, pre-administration with BBR suppressed the expression of pro-inflammatory factors (interleukin (IL)-6, IL-1β, cyclooxygenase (COX)-2 and tumor necrosis factor (TNF)-α) and the cell-proliferation marker Ki67, while expression of the tight junction proteins (ZO-1 and occludin) were increased in colon tissue. Moreover, the levels of critical pathway proteins involved in the inflammatory process (p-STAT3 and p-JNK) and cell cycle regulation molecules (β-catenin, c-Myc and CylinD1) exhibited lower expression levels. Besides, 16S rRNA sequence analysis indicated that pre-administration of BBR increased the ratio of Firmicutes/Bacteroidetes (F:M) and the relative abundance of potentially beneficial bacteria, while the abundance of cancer-related bacteria was decreased. Gavage with
can improve the anti-tumor effect of BBR. Overall, pre-administration of BBR exerts preventive effects in colon carcinogenesis, and the mechanisms underlying these effects are correlated with the inhibition of inflammation and tumor proliferation and the maintenance of intestinal homeostasis. |
| doi_str_mv | 10.3390/nu14040726 |
| format | Article |
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can improve the anti-tumor effect of BBR. Overall, pre-administration of BBR exerts preventive effects in colon carcinogenesis, and the mechanisms underlying these effects are correlated with the inhibition of inflammation and tumor proliferation and the maintenance of intestinal homeostasis.</description><identifier>ISSN: 2072-6643</identifier><identifier>EISSN: 2072-6643</identifier><identifier>DOI: 10.3390/nu14040726</identifier><identifier>PMID: 35215376</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; Azoxymethane ; Azoxymethane - toxicity ; Bacteria ; Berberine ; c-Myc protein ; Carcinogenesis ; Carcinogenesis - metabolism ; Carcinogens ; Cell cycle ; Cell growth ; Colitis ; Colitis - chemically induced ; Colitis - drug therapy ; Colitis - metabolism ; Colon ; Colon - metabolism ; Colon cancer ; Colorectal cancer ; Colorectal carcinoma ; Cyclooxygenase-2 ; Cytokines ; Dextran ; Dextran Sulfate - toxicity ; Dextrans ; Diet ; Disease Models, Animal ; Disease prevention ; Feeds ; Gastrointestinal Microbiome ; Homeostasis ; IL-1β ; Inflammation ; Inflammation - metabolism ; Inflammatory bowel disease ; Inflammatory diseases ; Intestinal microflora ; Intestine ; Malignancy ; Medical research ; Mice ; Mice, Inbred C57BL ; Microbiota ; Myc protein ; Natural products ; Pathogenesis ; Pathogens ; Prostaglandin endoperoxide synthase ; Proteins ; Relative abundance ; RNA, Ribosomal, 16S - metabolism ; rRNA 16S ; Sodium sulfate ; Stat3 protein ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; Tumorigenesis ; Tumors ; Weight loss ; Zonula occludens-1 protein ; β-Catenin</subject><ispartof>Nutrients, 2022-02, Vol.14 (4), p.726</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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Berberine (BBR) has attracted great attention in recent years due to its heath-related benefits in inflammatory disorders and tumors, but the intricate mechanisms have not been fully elucidated. In this study, the effects and the mechanism of BBR on colon cancer were investigated in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated carcinogenesis mice model. Our results showed that pre-administration of BBR showed a decrease in weight loss, disease activity index (DAI) score, and the number of colon tumors in mice, compared with the model group. The evidence from pathological examination indicated that the malignancy of intestinal tumors was ameliorated after pre-administration of BBR. Additionally, pre-administration with BBR suppressed the expression of pro-inflammatory factors (interleukin (IL)-6, IL-1β, cyclooxygenase (COX)-2 and tumor necrosis factor (TNF)-α) and the cell-proliferation marker Ki67, while expression of the tight junction proteins (ZO-1 and occludin) were increased in colon tissue. Moreover, the levels of critical pathway proteins involved in the inflammatory process (p-STAT3 and p-JNK) and cell cycle regulation molecules (β-catenin, c-Myc and CylinD1) exhibited lower expression levels. Besides, 16S rRNA sequence analysis indicated that pre-administration of BBR increased the ratio of Firmicutes/Bacteroidetes (F:M) and the relative abundance of potentially beneficial bacteria, while the abundance of cancer-related bacteria was decreased. Gavage with
can improve the anti-tumor effect of BBR. Overall, pre-administration of BBR exerts preventive effects in colon carcinogenesis, and the mechanisms underlying these effects are correlated with the inhibition of inflammation and tumor proliferation and the maintenance of intestinal homeostasis.</description><subject>Animals</subject><subject>Azoxymethane</subject><subject>Azoxymethane - toxicity</subject><subject>Bacteria</subject><subject>Berberine</subject><subject>c-Myc protein</subject><subject>Carcinogenesis</subject><subject>Carcinogenesis - metabolism</subject><subject>Carcinogens</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Colitis</subject><subject>Colitis - chemically induced</subject><subject>Colitis - drug therapy</subject><subject>Colitis - metabolism</subject><subject>Colon</subject><subject>Colon - metabolism</subject><subject>Colon cancer</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Cyclooxygenase-2</subject><subject>Cytokines</subject><subject>Dextran</subject><subject>Dextran Sulfate - toxicity</subject><subject>Dextrans</subject><subject>Diet</subject><subject>Disease Models, Animal</subject><subject>Disease prevention</subject><subject>Feeds</subject><subject>Gastrointestinal Microbiome</subject><subject>Homeostasis</subject><subject>IL-1β</subject><subject>Inflammation</subject><subject>Inflammation - metabolism</subject><subject>Inflammatory bowel disease</subject><subject>Inflammatory diseases</subject><subject>Intestinal microflora</subject><subject>Intestine</subject><subject>Malignancy</subject><subject>Medical research</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microbiota</subject><subject>Myc protein</subject><subject>Natural products</subject><subject>Pathogenesis</subject><subject>Pathogens</subject><subject>Prostaglandin endoperoxide synthase</subject><subject>Proteins</subject><subject>Relative abundance</subject><subject>RNA, Ribosomal, 16S - metabolism</subject><subject>rRNA 16S</subject><subject>Sodium sulfate</subject><subject>Stat3 protein</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><subject>Weight loss</subject><subject>Zonula occludens-1 protein</subject><subject>β-Catenin</subject><issn>2072-6643</issn><issn>2072-6643</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNpdks9u1DAQxiMEolXphQdAlrggpNBx_CebC9J2KbBSV0UqnC3HGW9dJfZiJyt4qT5jHW0pBV_G-uanzzOeKYrXFD4w1sCZnygHDnUlnxXHVY6llJw9f3I_Kk5TuoX51FBL9rI4YqKigtXyuLj7FrFcdoPzLo1Rjy54Eiw5x9hidB7JxS-MYyKrGxzCLuIe_ej2WbYWTdadJ8urzdmn6-ty7bvJYEdWoXejS-UypWCcHmdJR-N82KLH5BLZOINk7zTZhG7q86N-S9be9noYDhVo32VhxJRTup_5GFoXRv2qeGF1n_D0IZ4UPz5ffF99LS-vvqxXy8vScJBjSYFzIYTVYCjUndC1AQtgeasZaFzYTsq2Ym3NKmYEbwRARxE05RSZrhp2Unw8-O6mdsDO5K6j7tUuukHH3ypop_7NeHejtmGvFou6aTjLBu8eDGL4OeVG1OCSwb7XHsOUVCXz9ATQRmb07X_obZhi7vtAAeNiMRu-P1D5K1KKaB-LoaDmTVB_NyHDb56W_4j-mTu7Bx-_sSw</recordid><startdate>20220209</startdate><enddate>20220209</enddate><creator>Deng, Jiaqiang</creator><creator>Zhao, Lili</creator><creator>Yuan, Xieyong</creator><creator>Li, Yan</creator><creator>Shi, Junyang</creator><creator>Zhang, Hua</creator><creator>Zhao, Yuxuan</creator><creator>Han, Liping</creator><creator>Wang, Huani</creator><creator>Yan, Yan</creator><creator>Zhao, Hong</creator><creator>Wang, Haojie</creator><creator>Zou, Fangdong</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TS</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6496-0199</orcidid><orcidid>https://orcid.org/0000-0002-2133-4320</orcidid></search><sort><creationdate>20220209</creationdate><title>Pre-Administration of Berberine Exerts Chemopreventive Effects in AOM/DSS-Induced Colitis-Associated Carcinogenesis Mice via Modulating Inflammation and Intestinal Microbiota</title><author>Deng, Jiaqiang ; Zhao, Lili ; Yuan, Xieyong ; Li, Yan ; Shi, Junyang ; Zhang, Hua ; Zhao, Yuxuan ; Han, Liping ; Wang, Huani ; Yan, Yan ; Zhao, Hong ; Wang, Haojie ; Zou, Fangdong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-1044555fa0c107d5a7c0f00f4ba30ae8fd66b23b7323c549500d1e0a141e3a293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Azoxymethane</topic><topic>Azoxymethane - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nutrients</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Deng, Jiaqiang</au><au>Zhao, Lili</au><au>Yuan, Xieyong</au><au>Li, Yan</au><au>Shi, Junyang</au><au>Zhang, Hua</au><au>Zhao, Yuxuan</au><au>Han, Liping</au><au>Wang, Huani</au><au>Yan, Yan</au><au>Zhao, Hong</au><au>Wang, Haojie</au><au>Zou, Fangdong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pre-Administration of Berberine Exerts Chemopreventive Effects in AOM/DSS-Induced Colitis-Associated Carcinogenesis Mice via Modulating Inflammation and Intestinal Microbiota</atitle><jtitle>Nutrients</jtitle><addtitle>Nutrients</addtitle><date>2022-02-09</date><risdate>2022</risdate><volume>14</volume><issue>4</issue><spage>726</spage><pages>726-</pages><issn>2072-6643</issn><eissn>2072-6643</eissn><abstract>Inflammatory activation and intestinal flora imbalance play an essential role in the development and progression of colorectal cancer (CRC). Berberine (BBR) has attracted great attention in recent years due to its heath-related benefits in inflammatory disorders and tumors, but the intricate mechanisms have not been fully elucidated. In this study, the effects and the mechanism of BBR on colon cancer were investigated in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated carcinogenesis mice model. Our results showed that pre-administration of BBR showed a decrease in weight loss, disease activity index (DAI) score, and the number of colon tumors in mice, compared with the model group. The evidence from pathological examination indicated that the malignancy of intestinal tumors was ameliorated after pre-administration of BBR. Additionally, pre-administration with BBR suppressed the expression of pro-inflammatory factors (interleukin (IL)-6, IL-1β, cyclooxygenase (COX)-2 and tumor necrosis factor (TNF)-α) and the cell-proliferation marker Ki67, while expression of the tight junction proteins (ZO-1 and occludin) were increased in colon tissue. Moreover, the levels of critical pathway proteins involved in the inflammatory process (p-STAT3 and p-JNK) and cell cycle regulation molecules (β-catenin, c-Myc and CylinD1) exhibited lower expression levels. Besides, 16S rRNA sequence analysis indicated that pre-administration of BBR increased the ratio of Firmicutes/Bacteroidetes (F:M) and the relative abundance of potentially beneficial bacteria, while the abundance of cancer-related bacteria was decreased. Gavage with
can improve the anti-tumor effect of BBR. Overall, pre-administration of BBR exerts preventive effects in colon carcinogenesis, and the mechanisms underlying these effects are correlated with the inhibition of inflammation and tumor proliferation and the maintenance of intestinal homeostasis.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>35215376</pmid><doi>10.3390/nu14040726</doi><orcidid>https://orcid.org/0000-0001-6496-0199</orcidid><orcidid>https://orcid.org/0000-0002-2133-4320</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Nutrients, 2022-02, Vol.14 (4), p.726 |
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| subjects | Animals Azoxymethane Azoxymethane - toxicity Bacteria Berberine c-Myc protein Carcinogenesis Carcinogenesis - metabolism Carcinogens Cell cycle Cell growth Colitis Colitis - chemically induced Colitis - drug therapy Colitis - metabolism Colon Colon - metabolism Colon cancer Colorectal cancer Colorectal carcinoma Cyclooxygenase-2 Cytokines Dextran Dextran Sulfate - toxicity Dextrans Diet Disease Models, Animal Disease prevention Feeds Gastrointestinal Microbiome Homeostasis IL-1β Inflammation Inflammation - metabolism Inflammatory bowel disease Inflammatory diseases Intestinal microflora Intestine Malignancy Medical research Mice Mice, Inbred C57BL Microbiota Myc protein Natural products Pathogenesis Pathogens Prostaglandin endoperoxide synthase Proteins Relative abundance RNA, Ribosomal, 16S - metabolism rRNA 16S Sodium sulfate Stat3 protein Tumor necrosis factor-TNF Tumor necrosis factor-α Tumorigenesis Tumors Weight loss Zonula occludens-1 protein β-Catenin |
| title | Pre-Administration of Berberine Exerts Chemopreventive Effects in AOM/DSS-Induced Colitis-Associated Carcinogenesis Mice via Modulating Inflammation and Intestinal Microbiota |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T17%3A24%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Pre-Administration%20of%20Berberine%20Exerts%20Chemopreventive%20Effects%20in%20AOM/DSS-Induced%20Colitis-Associated%20Carcinogenesis%20Mice%20via%20Modulating%20Inflammation%20and%20Intestinal%20Microbiota&rft.jtitle=Nutrients&rft.au=Deng,%20Jiaqiang&rft.date=2022-02-09&rft.volume=14&rft.issue=4&rft.spage=726&rft.pages=726-&rft.issn=2072-6643&rft.eissn=2072-6643&rft_id=info:doi/10.3390/nu14040726&rft_dat=%3Cproquest_pubme%3E2633950196%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2633034583&rft_id=info:pmid/35215376&rfr_iscdi=true |