乳香萃取物透過抑制發炎相關路徑減緩AOM/DSS所誘發的大腸腫瘤生成

大腸直腸癌(colorectal cancer)逐漸成為全世界普遍盛行的癌症之一，流行病學研究指出發炎反應會加劇腫瘤的形成(tumorigenesis)，其中乳香樹脂在印度傳統醫學中常用於治療多種發炎相關的疾病，本實驗所使用的天然物是乳香超臨界二氧化碳(CO2)萃取物，乳香樹脂中的主要成分為boswellic acids，利用LC-MS/MS分析萃取物中含有四種boswellic acids，包括β-boswellic acid、acetyl-β-boswellic acid、11-keto-β-boswellic acid和acetyl-11-keto-β-boswellic acid，雖然boswellic acids已被認為具有抗腫瘤生成的潛力，然而其機制尚不明確。故本實驗將更進一步以AOM/DSS致癌模式評估乳香萃取物抑制小鼠腸道腫瘤形成之功效，結果顯示在給予乳香萃取物之後可顯著提升小鼠存活率以及減少腸道腫瘤的形成，且從腸道組織分析的結果可以看出攝食乳香萃取物能藉由抑制NF-κB及調節MAPKs進而降低發炎酵素inducible nitric oxide synthase (iNOS)和cyclooxygenase-2 (COX-2)等之蛋白質表現量，此外乳香萃取物也能藉由減少磷酸化之Akt和GSK3β及其下游的cyclin D1來抑制細胞之增生。另外，我們也觀察到AOM/DSS誘導之小鼠在給予乳香萃取物後，能增加腸道中梭菌目(Clostridiales)的含量以及減少擬桿菌目(Bacteroidales)之比例。綜合以上結果我們認為乳香萃取物具有可發展為預防結腸直腸癌膳食補充劑之潛力。

關鍵字

乳香；大腸癌；發炎； Azoxymethane/Dextran sulfate sodium (AOM/DSS) ；腸道菌

並列摘要

Colorectal cancer (CRC) become a worldwide public health problem. In the previous studies, inflammation-linked carcinogenesis is well accepted concept and is often observed. Boswellia serrata resin has been used in India traditional medicine to treat a variety of inflammatory-related diseases. The most significant components of its supercritical CO2 extraction analysis by LC-MS/MS are boswellic acids including β-boswellic acid, acetyl-β-boswellic acid, 11-keto-β-boswellic acid and acetyl-11-keto-β-boswellic acid. Although boswellic acids have been shown to be potential anti-tumorigenesis phytochemicals, but their mechanisms involved are not clear. In the present study, we investigated the chemopreventive effects of a Boswellia serrata (BS) extract on azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon tumorigenesis in ICR mice. We found that the treatment with BS extract can restore the shortening of the colon length, enhance the survival rate and reduce the colonic tumor growth. Western blot and histological analysis revealed that dietary BS extract could markedly reduce the protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), mitogen-activated protein kinases (MAPKs) and nuclear expression of NF-κB. Furthermore, BS extract reduced cell proliferation via inhibiting phosphorylation level of Akt, GSK3β and downregulation of cyclin D1. In addition, we also observed the changes on colonic microbiota after fed with BS extract that enhanced the ratio of Clostridiales and decreased abundance of Bacteroidales in AOM/DSS-treated mice. These results suggest that dietary administration of BS extract may alleviate colonic tumorigenesis.

並列關鍵字

Boswellia serrata (BS) ； colorectal cancer (CRC) ； inflammation ； Azoxymethane/Dextran sulfate sodium (AOM/DSS) ； gut microbiome

參考文獻

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乳香萃取物透過抑制發炎相關路徑減緩AOM/DSS所誘發的大腸腫瘤生成

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