Study on mechanism of Chanbao zhichuang suppository in treating hemorrhoids based on network pharmacology and metabolomics

GUO Chunfeng; JIANG Xin; CHENG Ruyang; LIU Shumin; XIE Chunxiang; LU Fang

doi:10.6039/j.issn.1001-0408.2025.13.12

您当前的位置：

首页 >

文章列表页 >

Study on mechanism of Chanbao zhichuang suppository in treating hemorrhoids based on network pharmacology and metabolomics

更新时间：2025-09-24

- Study on mechanism of Chanbao zhichuang suppository in treating hemorrhoids based on network pharmacology and metabolomics
- ZHONGGUO YAOFANG Vol. 36, Issue 13, Pages: 1622-1628(2025)
- 作者机构：
  
  1.黑龙江中医药大学附属第二医院哈南分院中医内科，哈尔滨　150040
  2.黑龙江中医药大学中医药研究院，哈尔滨　150040
  3.黑龙江蟾宝生物科技发展有限公司，黑龙江鹤岗　154100
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2025.13.12
  CLC： R965;R285
- Received：17 February 2025，
  
  Revised：2025-06-09，
  
  Accepted：10 June 2025，
  
  Published：15 July 2025
- 稿件说明：
移动端阅览
郭春风,蒋鑫,程汝阳,等.基于网络药理学和代谢组学的蟾宝痔疮栓抗痔疮的机制研究[J].中国药房,2025,36(13):1622-1628.

GUO Chunfeng,JIANG Xin,CHENG Ruyang,et al.Study on mechanism of Chanbao zhichuang suppository in treating hemorrhoids based on network pharmacology and metabolomics[J].ZHONGGUO YAOFANG,2025,36(13):1622-1628.
郭春风,蒋鑫,程汝阳,等.基于网络药理学和代谢组学的蟾宝痔疮栓抗痔疮的机制研究[J].中国药房,2025,36(13):1622-1628. DOI： 10.6039/j.issn.1001-0408.2025.13.12.

GUO Chunfeng,JIANG Xin,CHENG Ruyang,et al.Study on mechanism of Chanbao zhichuang suppository in treating hemorrhoids based on network pharmacology and metabolomics[J].ZHONGGUO YAOFANG,2025,36(13):1622-1628. DOI： 10.6039/j.issn.1001-0408.2025.13.12.

摘要

目的

通过网络药理学和代谢组学探讨蟾宝痔疮栓（CBZCS）对痔疮大鼠的改善作用机制。

方法

利用浸吸巴豆油致肛门肿胀建立大鼠痔疮模型。将SD大鼠分为空白组（NC组，0.32 g/kg凡士林），模型组（Model组，0.32 g/kg凡士林），CBZCS低、中、高剂量组（分别记为CBZCS-L、CBZCS-M、CBZCS-H组，给药剂量分别为0.16、0.32、0.64 g/kg），马应龙麝香痔疮栓组（Positive组，0.32 g/kg），每组9只；分别于造模后6、12、24、48、72 h进行肛门给药。末次给药后，观察大鼠肛门组织病理变化，检测大鼠血清中白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）水平。通过代谢组学的方法进行差异代谢物分析和通路富集分析，运用网络药理学获得CBZCS治疗痔疮的靶点蛋白，联合差异代谢物和靶点蛋白进行交互和富集分析以筛选核心代谢通路，并对核心蛋白进行实验验证。

结果

与NC组比较，Model组大鼠肛门组织出现明显病变，血清中IL-6、TNF-α水平显著升高（

＜0.05）；与Model组比较，给药组大鼠肛门组织病理损伤均有不同程度缓解，CBZCS-H组、CBZCS-M组、Positive组大鼠血清中IL-6水平和CBZCS-H组大鼠血清中TNF-α水平均显著降低（

＜0.05）。代谢组学结果显示，从大鼠的肛门组织中共筛选出34个差异代谢物，经CBZCS给药后共有22个出现回调。回调的差异代谢物主要富集于花生四烯酸代谢、组氨酸代谢和甘油磷脂代谢通路。通过网络药理学的方法确定了138个CBZCS抗痔疮的交集基因。差异代谢物和靶点蛋白主要富集于花生四烯酸代谢通路，该通路的调控可能与环氧合酶2（COX-2）、

Myc

原癌基因蛋白（c-MYC）、细胞色素P450 1B1（CYP1B1）、白细胞介素1β（IL-1β）、IL-6的蛋白表达有关。实验验证结果显示，Model组大鼠肛门组织中关键蛋白（COX-2、c-MYC、CYP1B1、IL-1β、IL-6）的表达水平均较NC组显著升高（

＜0.05），CBZCS-H组和Positive组大鼠肛门组织中上述蛋白水平均较Model组显著降低（

＜0.05）。

结论

CBZCS抗痔疮机制可能是抑制COX-2、c-MYC、CYP1B1蛋白的表达，进而抑制花生四烯酸代谢，减少炎症因子IL-6、IL-1β的释放。

Abstract

OBJECTIVE

To explore the mechanism of improvement effect of Chanbao zhichuang suppository （CBZCS） on hemorrhoids in rats through network pharmacology and metabolomics.

METHODS

A hemorrhoid model was established by subcutaneous injection of rhododendron oil to induce anal swelling. SD rats were divided into blank group （NC group， 0.32 g/kg vaseline）， model group （Model group， 0.32 g/kg vaseline）， CBZCS low-， medium-， and high-dose groups （CBZCS-L， CBZCS-M， CBZCS-H groups， with dosages of 0.16， 0.32， and 0.64 g/kg respectively）， and Mayinglong musk hemorrhoids suppository group （Positive group， 0.32 g/kg）， with 9 rats in each group. Anal administration was performed at 6， 12， 24， 48， and 72 hours after modeling. After the last administration， the pathological changes of the anal tissues in rats were observed， and the serum levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in rats were detected. Differential metabolite analysis and enrichment analysis were conducted by metabolomics methods， and the target proteins of CBZCS in treating hemorrhoids were obtained by network pharmacology. The core metabolic pathways were screened by interaction and enrichment analysis of differential metabolites and proteins， and the core proteins were experimentally verified.

RESULTS

Compared with the NC group， the anal tissues of the Model group showed obvious lesions， and the levels of IL-6 and TNF-α in the serum were significantly increased （

＜0.05）； compared with the Model group， the pathological damage of the anal tissues in the treatment groups was alleviated to varying degrees， and serum levels of IL-6 in CBZCS-H group， CBZCS-M group， and Positive group as well as serum levels of TNF-α in CBZCS-H group were significantly reduced （

＜0.05）. The metabolomics results showed that 34 differential metabolites were screened from the anal tissues of rats， and 22 of them showed a return after CBZCS administration. The differential metabolites mainly enriched in arachidonic acid metabolism， histidine metabolism， and glycerophospholipid metabolism. Through the network pharmacology， 138 intersection genes of CBZCS against hemorrhoids were determined. The analysis results showed that differential metabolites and target proteins were mainly enriched in the arachidonic acid metabolism pathway， and the regulation of this pathway might be related to cyclooxygenase-2 （COX-2），

Myc

proto-oncogene protein （c-MYC）， cytochrome P450 1B1 （CYP1B1）， interleukin-1β （IL-1β）， and IL-6 protein exp

ression. The experimental verification results showed that the expression levels of key proteins （COX-2， c-MYC， CYP1B1， IL-6， IL-1β） in the anal tissues of the Model group were significantly higher than those in the NC group （

＜0.05）， and the levels of the above proteins in the anal tissues of CBZCS-H group and Positive group were significantly lower than those in the Model group （

＜0.05）.

CONCLUSIONS

The mechanism of CBZCS in treating hemorrhoids may be to inhibit the expression of COX-2， c-MYC and CYP1B1 proteins， thereby inhibiting arachidonic acid metabolism and reducing the release of inflammatory factors IL-6 and IL-1β.

关键词

Keywords

references

陈平，田振国，周璐，等 . 湖北省城区居民肛肠疾病流行病学调查 [J ] . 中国医药科学， 2015 ， 5 （ 5 ）： 188 - 191 .

COSTANTINI T W ， DEREE J ， LOOMIS W ， et al . Phosphodiesterase inhibition attenuates alterations to the tight junction proteins occludin and ZO-1 in immunostimulated Caco-2 intestinal monolayers [J ] . Life Sci ， 2009 ， 84 （ 1/2 ）： 18 - 22 .

GODEBERGE P ， SHEIKH P ， LOHSIRIWAT V ， et al . Micronized purified flavonoid fraction in the treatment of hemorrhoidal disease [J ] . J Comp Eff Res ， 2021 ， 10 （ 10 ）： 801 - 813 .

谢珉宁，徐璇，张磊，等 . 混合痔中医辨证分型与流行病学特点的相关性研究 [J ] . 江苏中医药， 2016 ， 48 （ 11 ）： 38 - 40 .

程飞 . 西药联合云南白药痔疮膏外敷治疗痔疮的疗效观察 [J ] . 临床合理用药杂志， 2015 ， 8 （ 6 ）： 132 - 133 .

梁中洁，杨晓勤 . 代谢组学在生物信息学专业中的教学探讨 [J ] . 科学咨询， 2022 （ 22 ）： 98 - 100 .

孙科，李新，韩彦琪，等 . 消痔丸对巴豆油致肛门肿胀模型大鼠的药效及作用机制研究 [J ] . 中草药， 2023 ， 54 （ 20 ）： 6734 - 6742 .

窦建卫，彭湃 . 康痔栓对大鼠肛周肿胀及小鼠断尾出血的影响 [J ] . 中医外治杂志， 2018 ， 27 （ 4 ）： 5 - 6 .

LIPINSKI C A . Rule of five in 2015 and beyond：target and ligand structural limitations，ligand chemistry structure and drug discovery project decisions [J ] . Adv Drug Deliv Rev ， 2016 ， 101 ： 34 - 41 .

徐珊，窦燕，李小军，等 . 苦参凝胶对痔疮模型大鼠的治疗效果及机制研究 [J ] . 中医药学报， 2024 ， 52 （ 3 ）： 34 - 39 .

LEI C Q ， WU X ， ZHONG X ， et al . USP19 inhibits TNF-α- and IL-1β-triggered NF-κB activation by deubiquitina- ting TAK1 [J ] . J Immunol ， 2019 ， 203 （ 1 ）： 259 - 268 .

XUE Y R ， DENG Q Q ， ZHANG Q L ， et al . Gigantol ameliorates CCl 4 -induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway [J ] . Sci Rep ， 2020 ， 10 （ 1 ）： 22265 .

KAPRAL M ， WAWSZCZYK J ， SOŚNICKI S ， et al . Modulating effect of inositol hexaphosphate on arachidonic acid-dependent pathways in colon cancer cells [J ] . Prostaglandins Other Lipid Mediat ， 2017 ， 131 ： 41 - 48 .

ZHOU Q ， SUN H J ， LIU S M . Effects of total saponins from Dioscorea nipponica Makino on monosodium urate-induced M1-polarized macrophages through arachidonic acid signaling pathway：an in vitro study [J ] . Chin J Integr Med ， 2023 ， 29 （ 1 ）： 44 - 51 .

SIMON L S . Role and regulation of cyclooxygenase-2 during inflammation [J ] . Am J Med ， 1999 ， 106 （ 5B ）： 37S - 42S .

ZHANG H ， YAO X ， ZHANG D ， et al . Anti-hemorrhoidal activity of Lian-Zhi-San，a traditional Chinese medicine，in an experimental hemorrhoidal model in rats [J ] . J Integr Med ， 2021 ， 19 （ 1 ）： 42 - 49 .

LIU G Y ， LI D Y ， ZHANG L W ， et al . Phenformin down-regulates c-myc expression to suppress the expression of pro-inflammatory cytokines in keratinocytes [J ] . Cells ， 2022 ， 11 （ 15 ）： 2429 .

KLINK C ， BINNEBOSEL M ， KAMMER D ， et al . Hae- morrhoids are related to changes of cell function in mucosa and submucosa [J ] . Int J Colorectal Dis ， 2009 ， 24 （ 12 ）： 1389 - 1394 .

ZELLER K I ， ZHAO X D ， LEE C W H ， et al . Global mapping of c-Myc binding sites and target gene networks in human B cells [J ] . Proc Natl Acad Sci USA ， 2006 ， 103 （ 47 ）： 17834 - 17839 .

BOROS É ， HEGEDŰS Z ， KELLERMAYER Z ， et al . Global alteration of colonic microRNAome landscape associated with inflammatory bowel disease [J ] . Front Immunol ， 2022 ， 13 ： 991346 .

AGUNDEZ J A G . Cytochrome P450 gene polymorphism and cancer [J ] . Curr Drug Metab ， 2004 ， 5 （ 3 ）： 211 - 224 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Mechanism of joint injection of Caulophyllum robustum Maxim in the treatment of rheumatoid arthritis

Mechanism of Gexia zhuyu decoction in the intervention of metabolic-associated fatty liver disease by inhibiting ferroptosis

试析新药研发过程中的转化研究链

系统药理学研究方法在中药不良反应研究中的应用进展

Q-marker analysis of Kanggongyan soft capsule

Related Author

KUANG Haixue

GUO Yuyan

REN Yuhan

LIU Quanli

WU Yunyu

LYU Shaowa

YANG Jing

ZHAO Yuqiang

Related Institution

Key Laboratory of Basic and Applied Research of Northern Medicine， Ministry of Education， Heilongjiang University of Chinese Medicine/Heilongjiang Provincial Key Laboratory of Pharmacodynamic Substances of Traditional Chinese Medicine and Natural Medicine

School of Basic Medical Sciences， Heilongjiang University of Traditional Chinese Medicine

School of Pharmacy， Heilongjiang University of Traditional Chinese Medicine

Address：8th Floor, Sihuan Building, No. 129 Daping Main Street, Yuzhong District, Chongqing, China Postal code：400042
Technical support is provided by Beijing Founder Electronics co., LTD 渝ICP备15012710号公网安备50010302001817
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰