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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Betaine combined with traditional Chinese medicine ointment to treat skin wounds in microbially infected diabetic mice
Wen-Yan Xu, Yuan-Yuan Dai, Shi-Xian Yang, Hao Chen, Yan-Qiang Huang, Pei-Pei Luo, Zhong-Heng Wei
Wen-Yan Xu, Yuan-Yuan Dai, Yan-Qiang Huang, Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
Yuan-Yuan Dai, Shi-Xian Yang, Zhong-Heng Wei, Guangxi Clinical Medical Research Center for Hepatobiliary Diseases, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
Hao Chen, Department of Pathology, Wannan Medical College, Wuhu 241002, Anhui Province, China
Yan-Qiang Huang, Guangxi Zhuang Autonomous Region Engineering Research Center of Clinical Prevention and Control Technology and Leading Drug for Microorganisms with Drug Resistance in Border Ethnic Areas, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
Pei-Pei Luo, Department of Gastroenterology, Wujin People’s Hospital Affiliated to Jiangsu University, Changzhou 213004, Jiangsu Province, China
Co-first authors: Wen-Yan Xu and Yuan-Yuan Dai.
Co-corresponding authors: Pei-Pei Luo and Zhong-Heng Wei.
Author contributions: Xu WY and Dai YY performed the experiments and acquired and analyzed the data; Yang SX and Chen H interpreted the data; Xu WY, Huang YQ, Luo PP and Wei ZH wrote or guided the writing of the manuscript; all the authors approved the final version of the article. Xu WY and Dai YY contributed equally to this work as co-first authors. Luo PP and Wei ZH have played an equally important role in the completion of this study and the manuscript of the article. They worked together on experimental design and data analysis. Among them, Luo PP was responsible for directing the ointment preparation and general mouse wound treatment experiments and perfecting the manuscript mainly. Wei ZH was responsible for directing the test of minimum inhibitory concentrations, toxicity testing, diabetic mouse animal experiments and related follow-up testing. Finally, Luo PP and Wei ZH revised the manuscript after the submission.
Supported by Guangxi Science and Technology Major Projects, No. 2023AA20009; and National Natural Science Foundation of China, No. 32360035 and No. 32060018.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Youjiang Medical University for Nationalities.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: All data included in this study are available upon request by contact with the corresponding author at
luopeipei@wjrmyy.cn.
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: Zhong-Heng Wei, Professor, Guangxi Clinical Medical Research Center for Hepatobiliary Diseases, Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Zhongshan Second Road, Youjiang District, Baise 533000, Guangxi Zhuang Autonomous Region,
China.01118@ymun.edu.cn
Received: August 7, 2024
Revised: September 21, 2024
Accepted: October 24, 2024
Published online: January 15, 2025
Processing time: 115 Days and 18.7 Hours
BACKGROUND
Skin wounds are highly common in diabetic patients, and with increasing types of pathogenic bacteria and antibiotic resistance, wounds and infections in diabetic patients are difficult to treat and heal.
AIM
To explore the effects of betaine ointment (BO) in promoting the healing of skin wounds and reducing the inflammation and apoptosis of skin cells in microbially infected diabetic mice.
METHODS
By detecting the minimum inhibitory concentrations (MICs) of betaine and plant monomer components such as psoralen, we prepared BO with betaine as the main ingredient, blended it with traditional Chinese medicines such as gromwell root and psoralen, and evaluated its antibacterial effects and safety in vitro and in vivo. The skin infection wound models of ordinary mice and diabetic mice were constructed, and the OTC drugs mupirocin ointment and Zicao ointment were used as controls to evaluate the antibacterial effects in vivo and the anti-inflammatory and anti-apoptotic effects of BO.
RESULTS
The MICs of betaine against microorganisms such as Staphylococcus aureus (S. aureus), Candida albicans and Cryptococcus neoformans ranged from 4 to 32 μg/mL. Gromwell root and psoralea, both of which contain antimicrobial components, mixed to prepare BO with MICs ranging from 16 to 64 μg/mL, which is 32-256 times lower than those of Zicao ointment, although the MIC is greater than that of betaine. After 15 days of treatment with BO for USA300-infected ordinary mice, the wound scab removal rates were 83.3%, while those of mupirocin ointment and Zicao ointment were 66.7% and 0%, respectively, and the differences were statistically significant. In diabetic mice, the wound scab removal rate of BO and mupirolacin ointment was 80.0%, but BO reduced wound inflammation and the apoptosis of skin cells and facilitated wound healing.
CONCLUSION
The ointment prepared by mixing betaine and traditional Chinese medicine can effectively inhibit common skin microorganisms and has a strong effect on the skin wounds of sensitive or drug-resistant S. aureus-infected ordinary mice and diabetic mice.
Core Tip: Antibiotic ointments are commonly used to treat wounds in diabetic patients, but the antibacterial spectrum is narrow, resistance occurs easily or does not effectively inhibit drug-resistant bacteria, and wound healing is slow. The focus of this study was to determine whether some natural Chinese medicines and betaine could enhance the antimicrobial, anti-inflammatory, anti-apoptotic and accelerated wound healing effects of the ointment. Therefore, we generated a novel betaine ointment (BO) and evaluated its effects and safety. We found that BO could reduce the colonization of pathogens, inflammation and apoptosis and contribute to the proliferation of granulomas, which has good prospects for application.
