Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2023; 29(14): 2134-2152
Published online Apr 14, 2023. doi: 10.3748/wjg.v29.i14.2134
Anti-inflammatory effect and antihepatoma mechanism of carrimycin
Xiu-Yan Li, Yu-Ting Luo, Yan-Hong Wang, Zhi-Xin Yang, Yu-Zhou Shang, Qing-Xia Guan
Xiu-Yan Li, Yu-Ting Luo, Yan-Hong Wang, Zhi-Xin Yang, Yu-Zhou Shang, Qing-Xia Guan, Key Laboratory of Basic and Application Research of Beiyao, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
Author contributions: Li XY, Luo YT, Guan QX, Wang YH, Yang ZX, and Shang YZ performed the experiments and acquired and analyzed the data; Li XY and Luo YT wrote the manuscript; and all authors approved the final version of the article.
Supported by Heilongjiang Natural Science Foundation, No. LH2022H085 and H2016057; and Scientific Research Project of Heilongjiang Health Committee, No. 2020-293.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals (Scientific Research Project of Heilongjiang Health Committee, No. 2020-293).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Qing-Xia Guan, PhD, Teacher, Key Laboratory of Basic and Application Research of Beiyao, Heilongjiang University of Chinese Medicine, No. 24 Heping Road, Xiangfang District, Harbin 150040, Heilongjiang Province, China. 546105832@qq.com
Received: November 28, 2022
Peer-review started: November 28, 2022
First decision: December 20, 2022
Revised: December 29, 2022
Accepted: March 9, 2023
Article in press: March 9, 2023
Published online: April 14, 2023
Abstract
BACKGROUND

New drugs are urgently needed for the treatment of liver cancer, a feat that could be feasibly accomplished by finding new therapeutic purposes for marketed drugs to save time and costs. As a new class of national anti-infective drugs, carrimycin (CAM) has strong activity against gram-positive bacteria and no cross resistance with similar drugs. Studies have shown that the components of CAM have anticancer effects.

AIM

To obtain a deeper understanding of CAM, its distribution, metabolism and anti-inflammatory effects were assessed in the organs of mice, and its mechanism of action against liver cancer was predicted by a network pharmacology method.

METHODS

In this paper, the content of isovaleryl spiramycin III was used as an index to assess the distribution and metabolism of CAM and its effect on inflammatory factors in various mouse tissues and organs. Reverse molecular docking technology was utilized to determine the target of CAM, identify each target protein based on disease type, and establish a target protein-disease type network to ascertain the effect of CAM in liver cancer. Then, the key action targets of CAM in liver cancer were screened by a network pharmacology method, and the core targets were verified by molecular docking and visual analyses.

RESULTS

The maximum CAM concentration was reached in the liver, kidney, lung and spleen 2.5 h after intragastric administration. In the intestine, the maximum drug concentration was reached 0.5 h after administration. In addition, CAM significantly reduced the interleukin-4 (IL-4) levels in the lung and kidney and especially the liver and spleen; moreover, CAM significantly reduced the IL-1β levels in the spleen, liver, and kidney and particularly the small intestine and lung. CAM is predicted to regulate related pathways by acting on many targets, such as albumin, estrogen receptor 1, epidermal growth factor receptor and caspase 3, to treat cancer, inflammation and other diseases.

CONCLUSION

We determined that CAM inhibited inflammation. We also predicted the complex multitargeted effects of CAM that involve multiple pathways and the diversity of these effects in the treatment of liver cancer, which provides a basis and direction for further clinical research.

Keywords: Carrimycin, Reverse molecular docking, Network pharmacology, Liver cancer, Anti-inflammatory, Anti-hepatoma

Core Tip: Although some studies have shown that carrimycin (CAM) has therapeutic effects on inflammation and liver cancer, there are few experimental studies on its component analysis and mechanism of action. The mechanism of action was predicted by reverse molecular docking between the liver cancer target and CAM. By establishing an inflammatory mouse model to assess the state of inflammatory factors after administration, we further proved the therapeutic effect of CAM on inflammation and its possible mechanism in the treatment of liver cancer.