title: Palmatine from Mahonia bealei attenuates gut tumorigenesis in ApcMin/+ mice via inhibition of inflammatory cytokines.
abstract: Mahonia bealei is a Chinese folk medicine used to treat various ailments, in particular gastrointestinal inflammation‑related illnesses, and palmatine is one of its active constituents. In this study, ApcMin/+ mice, a genetically engineered model, were used to investigate the effects of palmatine on the initiation and progression of gut inflammation and tumorigenesis enhanced by a high‑fat diet. The in vitro antiproliferation and anti‑inflammation effects of palmatine were evaluated on HT‑29 and SW‑480 human colorectal cancer cell lines. The concentration‑related antiproliferative effects of palmatine on both cell lines (P<0.01) were observed. Palmatine significantly inhibited lipopolysaccharide‑induced increase in cytokine interleukin (IL)‑8 levels in the HT‑29 cells (P<0.01). In the in vivo studies with ApcMin/+ mice, after 10 or 20 mg/kg/day oral palmatine treatment, tumor numbers were significantly reduced in the small intestine and colon in a dose‑dependent manner (P<0.01 compared with the model group). The results were supported by tumor distribution data, body weight changes and organ index. The effect on survival was also dose‑dependent. Both the low‑ and high‑dose palmatine treatments significantly increased the life span of the mice (P<0.01). The gut histology from the model group showed a prominent adenomatous change along with inflammatory lesions. With palmatine treatment, however, the dysplastic changes were greatly reduced in the small intestine and colon tissue. Reverse transcription‑quantitative polymerase chain reaction analysis of interleukin (IL)‑1α, IL1‑β, IL‑8, granulocyte‑colony stimulating factor and granulocyte macrophage colony‑stimulating factor in the gut tissue showed that these inflammatory cytokines were reduced significantly following treatment (all P<0.01); serum cytokine levels were also decreased. Data suggests that palmatine has a clinical value in colorectal cancer therapeutics, and this action is likely linked to the inhibition of inflammatory cytokines.
authors.affiliation: Teaching and Research Section of Traditional Chinese Pharmaceutics, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Wei-Kun
authors.initials: WK
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Traditional Chinese Medicine, People's Hospital of Zhangqiu, Zhangqiu, Jinan, Shandong 250200, P.R. China.
authors.forename: Cui-Lan
authors.initials: CL
authors.lastname: Dong
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: He
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Chang-Run
authors.initials: CR
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Zhang
authors.affiliation: Tang Center of Herbal Medicine Research and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Chun-Hao
authors.initials: CH
authors.lastname: Yu
authors.affiliation: Tang Center of Herbal Medicine Research and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Wang
authors.affiliation: Tang Center of Herbal Medicine Research and Department of Anesthesia and Critical Care, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Chun-Su
authors.initials: CS
authors.lastname: Yuan
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000097:blood / Q000235:genetics*; D000818:Animals; D001600:Berberine Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D028143:Mahonia / Q000737:chemistry*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D001600:Berberine Alkaloids; D016207:Cytokines; D018836:Inflammation Mediators; D010936:Plant Extracts; C005413:palmatine