

浏览全部资源
扫码关注微信
上海中医药大学 附属曙光医院,上海 201203
Received:13 October 2022,
Published Online:13 February 2023,
Published:20 February 2024
移动端阅览
张平平,贾茹,岑戎等.败酱草中黄酮类化学成分影响大肠癌发生发展的作用机制研究进展[J].中国实验方剂学杂志,2024,30(04):240-247.
ZHNAG Pingping,JIA Ru,CEN Rong,et al.Mechanism of Flavonoids in Patriniae Herba in Affecting Occurrence and Development of Colorectal Cancer[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(04):240-247.
张平平,贾茹,岑戎等.败酱草中黄酮类化学成分影响大肠癌发生发展的作用机制研究进展[J].中国实验方剂学杂志,2024,30(04):240-247. DOI: 10.13422/j.cnki.syfjx.20230825.
ZHNAG Pingping,JIA Ru,CEN Rong,et al.Mechanism of Flavonoids in Patriniae Herba in Affecting Occurrence and Development of Colorectal Cancer[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(04):240-247. DOI: 10.13422/j.cnki.syfjx.20230825.
大肠癌是消化系统常见恶性肿瘤,居全球癌症发病谱第3位和死因谱第2位。近年来大肠癌发病率呈上升趋势,发病年龄呈现年轻化,癌症负担沉重,因此防治大肠癌发生发展及复发转移对降低大肠癌发病率和死亡率具有重要意义。败酱草具有清热解毒、消痈排脓的功效,对炎性肠病、消化道肿瘤、盆腔炎症、妇科肿瘤等多种疾病具有良好的疗效。临床常应用败酱草治疗大肠癌,但其作用机制尚不完全清楚。现代研究发现败酱草含有三萜类、皂苷、环烯醚萜类、黄酮类等多种化学成分,具有抗氧化、抗肿瘤、抗菌、抗病毒等多种药理作用,其中黄酮类化学成分是败酱草主要抗肿瘤成分,网络药理及谱效关系分析认为,槲皮素、木犀草素、芹菜素、异牡荆素、异红草苷在败酱草抑制大肠癌发生发展过程中起主要作用。体内外研究显示,败酱草中黄酮类化学成分可以从防止大肠癌癌前病变、抑制癌细胞生长增殖、阻滞癌细胞周期、促进癌细胞凋亡、逆转大肠癌耐药等多种途径发挥抗肿瘤作用。黄酮类化合物口服利用度低,肠道是黄酮类化合物在体内的主要代谢部位,其代谢途径与肠道微生物关系密切。该文对败酱草中主要黄酮类化学成分抗肿瘤机制及其对肠道微生物群影响相关研究做一综述,以期为深入研究败酱草抗大肠癌作用机制、转化临床应用提供研究思路。
Colorectal cancer is a common malignant tumor in the digestive system, ranking third in incidence and second in the cause of death worldwide. In recent years, the incidence of colorectal cancer is on the rise, and the age of patients with colorectal cancer tends to be younger, with a heavy cancer burden. It is of great significance to prevent the occurrence, development, recurrence, and metastasis of colorectal cancer to reduce the incidence and mortality of colorectal cancer. Patriniae Herba has the effects of clearing heat, removing toxins, eliminating carbuncle, and discharging pus and shows good therapeutic efficacy on inflammatory bowel disease, digestive tract tumors, pelvic inflammation, gynecological tumor, and so on. Patriniae Herba
is often used in the clinical treatment of colorectal cancer, but its mechanism of action is not clear. Modern studies have found that Patriniae Herba
contains triterpenoids, saponins, iridoids, flavonoids, and other chemical components, with antioxidant, anti-tumor, anti-bacterial, and other pharmacological effects. The main anti-tumor components of Patriniae Herba
are flavonoids. The analysis of network pharmacology and the spectrum-effect relationship has suggested that quercetin, luteolin, apigenin, isoorientin, and isovitexin play a major role in inhibiting the occurrence and development of colorectal cancer.
In vivo
and
in vitro
studies have shown that flavonoids in Patriniae Herba can play an anti-tumor role in various ways, such as preventing precancerous lesions of colorectal cancer, inhibiting the growth and proliferation of cancer cells, blocking cancer cell cycle, promoting cancer cell apoptosis, and reversing drug resistance of colorectal cancer. The oral availability of flavonoids is low. The gut is the main metabolic site of flavonoids in the body, its metabolic pathway is closely related to gut microbiota. This paper reviewed the anti-tumor mechanism of flavonoids and their influence on gut microbiota to provide a reference for further research on the mechanism of Patriniae Herba against colorectal cancer and its clinical application.
SUNG H , FERLAY J , SIEGEL R L , et al . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin , 2021 , 71 ( 3 ): 209 - 249 .
ZHENG R , ZHANG S , ZENG H , et al . Cancer incidence and mortality in China, 2016 [J]. J Nat Can Cen , 2022 , 2 ( 1 ): 1 - 9 .
范宇 , 沙冬梅 , 沙马里牛 , 等 . 白花败酱草的化学成分、药理活性及质量控制研究进展 [J]. 中国中药杂志 , 2022 , 47 ( 22 ): 6005 - 6019 .
赵桢 , 徐佳越 , 刘少璇 , 等 . 黄酮类中药单体对卵巢癌信号通路调控作用的研究进展 [J]. 中国实验方剂学杂志 , 2022 , 28 ( 19 ): 222 - 230 .
LIU L , SHEN A , CHEN Y , et al . Patrinia scabiosaefolia induces mitochondrial-dependent apoptosis in a mouse model of colorectal cancer [J]. Oncol Rep , 2013 , 30 ( 2 ): 897 - 903 .
ZHANG M , SUN G , SHEN A , et al . Patrinia scabiosaefolia inhibits the proliferation of colorectal cancer in vitro and in vivo via G 1 /S cell cycle arrest [J]. Oncol Rep , 2015 , 33 ( 2 ): 856 - 860 .
HUANG S Z , LIU W Y , HUANG Y , et al . Patrinia scabiosaefolia inhibits growth of 5-FU-resistant colorectal carcinoma cells via induction of apoptosis and suppression of Akt pathway [J]. Chin J Integr Med , 2019 , 25 ( 2 ): 116 - 121 .
CHEN L , LIU L , YE L , et al . Patrinia scabiosaefolia inhibits colorectal cancer growth through suppression of tumor angiogenesis [J]. Oncol Rep , 2013 , 30 ( 3 ): 1439 - 1443 .
邹鑫 , 余霞 , 付加伟 , 等 . 薏苡附子败酱散对结肠癌细胞HCT116凋亡的影响及机制 [J]. 中国实验方剂学杂志 , 2023 , 29 ( 21 ): 41 - 48 .
魏一萌 , 王帅 , 孟宪生 , 等 . 基于SMMC-7721肝癌细胞生长抑制的两种败酱草药效比较及提取方法研究 [J]. 中国医药科学 , 2013 , 3 ( 11 ): 35 - 37 .
GONG L , ZOU W , ZHENG K , et al . The Herba Patriniae (Caprifoliaceae): A review on traditional uses, phytochemistry, pharmacology and quality control [J]. J Ethnopharmacol , 2021 , doi: 10.1016/j.jep.2020.113264 http://dx.doi.org/10.1016/j.jep.2020.113264 .
周丽萍 , 韩啸 , 李晓晨 , 等 . 基于谱效关系的白花败酱草黄酮部位抗肠肿瘤活性成分筛选研究 [J]. 亚太传统医药 , 2021 , 17 ( 6 ): 45 - 48 .
丁昕瑶 , 王帅 , 李天娇 , 等 . 基于细胞凋亡芯片的白花败酱草乙酸乙酯部位抗结肠癌的物质基础研究 [J]. 中南药学 , 2022 , 20 ( 3 ): 537 - 543 .
吴梦雪 , 彭涛 , 崔亚新 , 等 . 基于网络药理学探讨败酱草治疗大肠癌的作用机制 [J]. 河南中医 , 2021 , 41 ( 5 ): 780 - 784 .
CLAPPER M L , CHANG W L , COOPER H S . Dysplastic aberrant crypt foci: Biomarkers of early colorectal neoplasia and response to preventive intervention [J]. Cancer Prev Res (Phila) , 2020 , 13 ( 3 ): 229 - 240 .
GEE J M , HARA H , JOHNSON I T . Suppression of intestinal crypt cell proliferation and aberrant crypt foci by dietary quercetin in rats [J]. Nutr Cancer , 2002 , 43 ( 2 ): 193 - 201 .
WARREN C A , PAULHILL K J , DAVIDSON L A , et al . Quercetin may suppress rat aberrant crypt foci formation by suppressing inflammatory mediators that influence proliferation and apoptosis [J]. J Nutr , 2009 , 139 ( 1 ): 101 - 105 .
TANAKA T , KAWABATA K , HONJO S , et al . Inhibition of azoxymethane-induced aberrant crypt foci in rats by natural compounds, caffeine, quercetin and morin [J]. Oncol Rep , 1999 , 6 ( 6 ): 1333 - 1340 .
DIHAL A A , DE BOER V C , VAN DER WOUDE H , et al . Quercetin, but not its glycosidated conjugate rutin, inhibits azoxymethane-induced colorectal carcinogenesis in F344 rats [J]. J Nutr , 2006 , 136 ( 11 ): 2862 - 2867 .
VOLATE S R , DAVENPORT D M , MUGA S J , et al . Modulation of aberrant crypt foci and apoptosis by dietary herbal supplements (quercetin, curcumin, silymarin, ginseng and rutin) [J]. Carcinogenesis , 2005 , 26 ( 8 ): 1450 - 1456 .
BENITO I , ENCÍO I J , MILAGRO F I , et al . Microencapsulated bifidobacterium bifidum and lactobacillus gasseri in combination with quercetin inhibit colorectal cancer development in Apc(Min/+) mice [J]. Int J Mol Sci , 2021 , doi: 10.3390/ijms22094906 http://dx.doi.org/10.3390/ijms22094906 .
ASHOKKUMAR P , SUDHANDIRAN G . Protective role of luteolin on the status of lipid peroxidation and antioxidant defense against azoxymethane-induced experimental colon carcinogenesis [J]. Biomed Pharmacother , 2008 , 62 ( 9 ): 590 - 597 .
AI X Y , QIN Y , LIU H J , et al . Apigenin inhibits colonic inflammation and tumorigenesis by suppressing STAT3-NF- κ B signaling [J]. Oncotarget , 2017 , 8 ( 59 ): 100216 - 100226 .
YANG L , LIU Y , WANG M , et al . Quercetin-induced apoptosis of HT-29 colon cancer cells via inhibition of the Akt-CSN6-Myc signaling axis [J]. Mol Med Rep , 2016 , 14 ( 5 ): 4559 - 4566 .
REFOLO M G , D'ALESSANDRO R , MALERBA N , et al . Anti proliferative and pro apoptotic effects of flavonoid quercetin are mediated by CB1 receptor in human colon cancer cell lines [J]. J Cell Physiol , 2015 , 230 ( 12 ): 2973 - 2980 .
MANJU V , NALINI N . Protective role of luteolin in 1,2-dimethylhydrazine induced experimental colon carcinogenesis [J]. Cell Biochem Funct , 2007 , 25 ( 2 ): 189 - 194 .
LIM D Y , JEONG Y , TYNER A L , et al . Induction of cell cycle arrest and apoptosis in HT-29 human colon cancer cells by the dietary compound luteolin [J]. Am J Physiol Gastrointest Liver Physiol , 2007 , 292 ( 1 ): 66 - 75 .
WANG W , HEIDEMAN L , CHUNG C S , et al . Cell-cycle arrest at G 2 /M and growth inhibition by apigenin in human colon carcinoma cell lines [J]. Mol Carcinog , 2000 , 28 ( 2 ): 102 - 110 .
CHENG Y , HAN X , MO F , et al . Apigenin inhibits the growth of colorectal cancer through down-regulation of E2F1/3 by miRNA-215-5p [J]. Phytomedicine , 2021 , doi: 10.1016/j.phymed.2021.153603 http://dx.doi.org/10.1016/j.phymed.2021.153603 .
GUNDOGDU G , DODURGA Y , ELMAS L , et al . Investigation of the anticancer mechanism of isoorientin isolated from eremurus spectabilis leaves via cell cycle pathways in HT-29 human colorectal adenocarcinoma cells [J]. Eurasian J Med , 2018 , 50 ( 3 ): 168 - 172 .
SHREE A , ISLAM J , SULTANA S . Quercetin ameliorates reactive oxygen species generation, inflammation, mucus depletion, goblet disintegration, and tumor multiplicity in colon cancer: Probable role of adenomatous polyposis coli, β -catenin [J]. Phytother Res , 2021 , 35 ( 4 ): 2171 - 2184 .
ÖZSOY S , BECER E , KABADAYI H , et al . Quercetin-mediated apoptosis and cellular senescence in human colon cancer [J]. Anticancer Agents Med Chem , 2020 , 20 ( 11 ): 1387 - 1396 .
YANG Y , WANG T , CHEN D , et al . Quercetin preferentially induces apoptosis in KRAS-mutant colorectal cancer cells via JNK signaling pathways [J]. Cell Biol Int , 2019 , 43 ( 2 ): 117 - 124 .
KRIFA M , LELOUP L , GHEDIRA K , et al . Luteolin induces apoptosis in BE colorectal cancer cells by downregulating calpain, UHRF1, and DNMT1 expressions [J]. Nutr Cancer , 2014 , 66 ( 7 ): 1220 - 1227 .
LIM D Y , CHO H J , KIM J , et al . Luteolin decreases IGF-Ⅱ production and downregulates insulin-like growth factor-Ⅰ receptor signaling in HT-29 human colon cancer cells [J]. BMC Gastroenterol , 2012 , doi: 10.1186/1471-230X-12-9 http://dx.doi.org/10.1186/1471-230X-12-9 .
ZHU H , ZHAO N , JIANG M . Isovitexin attenuates tumor growth in human colon cancer cells through the modulation of apoptosis and epithelial-mesenchymal transition via PI3K/Akt/mTOR signaling pathway [J]. Biochem Cell Biol , 2021 , 99 ( 6 ): 741 - 749 .
CHUNG C S , JIANG Y , CHENG D , et al . Impact of adenomatous polyposis coli (APC) tumor supressor gene in human colon cancer cell lines on cell cycle arrest by apigenin [J]. Mol Carcinog , 2007 , 46 ( 9 ): 773 - 782 .
ZHANG X , ZHANG W , CHEN F , et al . Combined effect of chrysin and apigenin on inhibiting the development and progression of colorectal cancer by suppressing the activity of p38-MAPK/Akt pathway [J]. IUBMB Life , 2021 , 73 ( 5 ): 774 - 783 .
XU M , WANG S , SONG Y U , et al . Apigenin suppresses colorectal cancer cell proliferation, migration and invasion via inhibition of the Wnt/ β -catenin signaling pathway [J]. Oncol Lett , 2016 , 11 ( 5 ): 3075 - 3080 .
CHUNHUA L , DONGLAN L , XIUQIONG F , et al . Apigenin up-regulates transgelin and inhibits invasion and migration of colorectal cancer through decreased phosphorylation of Akt [J]. J Nutr Biochem , 2013 , 24 ( 10 ): 1766 - 1775 .
DAI J , VAN WIE P G , FAI L Y , et al . Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells [J]. Toxicol Appl Pharmacol , 2016 , 311 : 106 - 112 .
NASO L G , BADIOLA I , MARQUEZ CLAVIJO J , et al . Inhibition of the metastatic progression of breast and colorectal cancer in vitro and in vivo in murine model by the oxidovanadium(Ⅳ) complex with luteolin [J]. Bioorg Med Chem , 2016 , 24 ( 22 ): 6004 - 6011 .
ZHOU Y , ZHANG J , WANG K , et al . Quercetin overcomes colon cancer cells resistance to chemotherapy by inhibiting solute carrier family 1, member 5 transporter [J]. Eur J Pharmacol , 2020 , doi: 10.1016/j.ejphar.2020.173185 http://dx.doi.org/10.1016/j.ejphar.2020.173185 .
LI Q C , LIANG Y , HU G R , et al . Enhanced therapeutic efficacy and amelioration of cisplatin-induced nephrotoxicity by quercetin in 1,2-dimethyl hydrazine-induced colon cancer in rats [J]. Indian J Pharmacol , 2016 , 48 ( 2 ): 168 - 171 .
SHARMA A , SINHA S , RATHAUR P , et al . Reckoning apigenin and kaempferol as a potential multi-targeted inhibitor of EGFR/HER2-MEK pathway of metastatic colorectal cancer identified using rigorous computational workflow [J]. Mol Divers , 2022 , 26 ( 6 ): 3337 - 3356 .
CHEN X , XU H , YU X , et al . Apigenin inhibits in vitro and in vivo tumorigenesis in cisplatin-resistant colon cancer cells by inducing autophagy, programmed cell death and targeting m-TOR/PI3K/Akt signalling pathway [J]. J Buon , 2019 , 24 ( 2 ): 488 - 493 .
PANDURANGAN A K , DHARMALINGAM P , SADAGOPAN S K , et al . Luteolin inhibits matrix metalloproteinase 9 and 2 in azoxymethane-induced colon carcinogenesis [J]. Hum Exp Toxicol , 2014 , 33 ( 11 ): 1176 - 1185 .
AU A , LI B , WANG W , et al . Effect of dietary apigenin on colonic ornithine decarboxylase activity, aberrant crypt foci formation, and tumorigenesis in different experimental models [J]. Nutr Cancer , 2006 , 54 ( 2 ): 243 - 251 .
XIAO J , CAPANOGLU E , JASSBI A R , et al . Advance on the flavonoid C-glycosides and health benefits [J]. Crit Rev Food Sci Nutr , 2016 , 56 ( Suppl 1 ): 29 - 45 .
MARÍN L , MIGUÉLEZ E M , VILLAR C J , et al . Bioavailability of dietary polyphenols and gut microbiota metabolism: Antimicrobial properties [J]. Biomed Res Int , 2015 , doi: 10.1155/2015/905215 http://dx.doi.org/10.1155/2015/905215 .
ROWLAND I , GIBSON G , HEINKEN A , et al . Gut microbiota functions: Metabolism of nutrients and other food components [J]. Eur J Nutr , 2018 , 57 ( 1 ): 1 - 24 .
ZHANG Y , TIE X , BAO B , et al . Metabolism of flavone C-glucosides and p-coumaric acid from antioxidant of bamboo leaves (AOB) in rats [J]. Br J Nutr , 2007 , 97 ( 3 ): 484 - 494 .
BRAUNE A , BLAUT M . Intestinal bacterium Eubacterium cellulosolvens deglycosylates flavonoid C -and O -glucosides [J]. Appl Environ Microbiol , 2012 , 78 ( 22 ): 8151 - 8153 .
WANG M , FIRRMAN J , LIU L , et al . A review on flavonoid apigenin: Dietary intake, ADME, antimicrobial effects, and interactions with human Gut microbiota [J]. Biomed Res Int , 2019 , doi: 10.1155/2019/7010467 http://dx.doi.org/10.1155/2019/7010467 .
苏镶月 , 崔刚 , 张波 , 等 . 黄酮类化合物调节肠道菌群的研究进展 [J]. 广东化工 , 2022 , 49 ( 6 ): 116 - 117,122 .
杨文博 , 彭丹 , 曹思邈 , 等 . 微生物合成黄酮类化合物研究进展 [J]. 生命科学 , 2022 , 34 ( 2 ): 220 - 227 .
李涛 , 李绮丽 , 张群 , 等 . 基于肠道菌群的黄酮类化合物生理功能研究进展 [J]. 中国食品学报 , 2022 , 22 ( 2 ): 357 - 368 .
TAO J , LI S , GAN R Y , et al . Targeting gut microbiota with dietary components on cancer: Effects and potential mechanisms of action [J]. Crit Rev Food Sci Nutr , 2020 , 60 ( 6 ): 1025 - 1037 .
DUDA-CHODAK A , TARKO T , SATORA P , et al . Interaction of dietary compounds, especially polyphenols, with the intestinal microbiota: A review [J]. Eur J Nutr , 2015 , 54 ( 3 ): 325 - 341 .
QU Y , LI X , XU F , et al . Kaempferol alleviates murine experimental colitis by restoring Gut microbiota and inhibiting the LPS-TLR4-NF- κ B axis [J]. Front Immunol , 2021 , doi: 10.3389/fimmu.2021.679897 http://dx.doi.org/10.3389/fimmu.2021.679897 .
0
Views
147
下载量
2
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621