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ORIGINAL RESEARCH article

Front. Microbiol.
Sec. Infectious Agents and Disease
Volume 15 - 2024 | doi: 10.3389/fmicb.2024.1491169

Aloe-emodin plus TIENAM ameliorate cecal ligation and puncture-induced sepsis in mice by attenuating inflammation and modulating microbiota

Provisionally accepted
Jingqian Su Jingqian Su 1*Xiaohui Deng Xiaohui Deng 1Shan Hu Shan Hu 1Xinrui Lin Xinrui Lin 1Lian Xie Lian Xie 1Hui Ye Hui Ye 1Congfan Lin Congfan Lin 1Fen Zhou Fen Zhou 1Shun Wu Shun Wu 1Liling Zheng Liling Zheng 2
  • 1 Fujian Normal University, Fuzhou, China
  • 2 Quanzhou First Hospital, Fujian Medical University, Quanzhou, Fujian Province, China

The final, formatted version of the article will be published soon.

    Despite the high sepsis-associated mortality, effective and specific treatments remain limited. Using conventional antibiotics as TIENAM (imipenem and cilastatin sodium for injection, TIE) is challenging due to increasing bacterial resistance, diminishing their efficacy and leading to adverse effects. We previously found that aloe-emodin (AE) exerts therapeutic effects on sepsis by reducing systemic inflammation and regulating the gut microbiota. Here, we investigated whether administering AE and TIE post-sepsis onset, using a cecal ligation and puncture (CLP)-induced sepsis model, extends survival and improves physiological functions. Survival rates, inflammatory cytokines, tissue damage, immune cell populations, ascitic fluid microbiota, and key signaling pathways were assessed. Combining AE and TIE significantly enhanced survival rates, and reduced inflammation and bacterial load in septic mice, indicating potent antimicrobial properties. Moreover, substantial improvements in survival rates of AE + TIE-treated mice (10% to 60%) within 168 h were observed relative to the CLP group. This combination therapy also effectively modulated inflammatory marker (interleukin [IL]-6, IL-1β, and tumor necrosis factor[TNF]-α) levels and immune cell counts by decreasing those of B, NK, and TNFR2 + Treg cells, while increasing that of CD8 + T cells; alleviated tissue damage; reduced bacterial load in the peritoneal cavity; and suppressed the NF-κB signaling pathway.We also observed a significantly altered peritoneal cavity microbiota composition Abbreviations: AE, Aloe-emodin; CLP, cecal ligation and puncture; LPS, lipopolysaccharide; MSS, murine sepsis score; TIE, TIENAM post-treatment, characterized by reduced pathogenic bacteria (Bacteroides) abundance. Our findings underscore the potential of AE + TIE in treating sepsis, and encourage further research and possible clinical implementations to surmount the limitations of TIE and amplify the therapeutic potential of AE.

    Keywords: Aloe-emodin, tienam, Sepsis, anti-inflammatory, combination therapy, peritoneal cavity microbiota

    Received: 04 Sep 2024; Accepted: 03 Dec 2024.

    Copyright: © 2024 Su, Deng, Hu, Lin, Xie, Ye, Lin, Zhou, Wu and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jingqian Su, Fujian Normal University, Fuzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.