A research team jointly led by Elaine Leung Lai Han, professor in the Faculty of Health Sciences (FHS) of the University of Macau (UM); Xie Ying, professor at the Second Affiliated Hospital of the Guangzhou University of Chinese Medicine; and Chen Jianxin, professor at the Beijing University of Chinese Medicine has discovered that the modern herbal formula BaWeiBaiDuSan (BWBDS) can help alleviate sepsis-induced liver injury (SILI). The study has received considerable attention in the field of pharmacology and the research results have been published in the internationally-renowned journal Acta Pharmaceutica Sinica B.

Sepsis is widely perceived as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Antibiotics are an essential component of initial therapy in sepsis. However, the inappropriate use of antibiotics can lead to multidrug-resistant infections and death. It is necessary to discover novel targeted or combined therapeutic strategies. The gut-liver axis refers to the bidirectional relationship of microbiota, metabolic, and immune crosstalks between the gut and liver, connected in a bidirectional fashion by the portal vein and biliary tree. SILI is related to adverse clinical outcomes and gut microbiota plays a crucial role in SILI. The formula BWBDS is based on components extracted from eight medicinal herbs, namely Panax ginseng C. A. Meyer, Lilium brownii F. E. Brown ex Miellez var. viridulum Baker, Polygonatum sibiricum Delar. ex Redoute, Lonicera japonica Thunb., Hippophae rhamnoides Linn, Amygdalus Communis Vas, Platycodon grandiflorus (Jacq.) A. DC., and Cortex Phellodendri. Previous studies by the team have showed that traditional Chinese medicine (TCM) formulas with medicine food homology can improve intestinal microecology and enhance host immune function. Therefore, in the study, the team investigated whether the BWBDS treatment could reverse SILI by modulating the gut microbiota. The study shows that BWBDS and L. johnsonii may act as prebiotics and probiotics for the prevention and treatment of sepsis.

Although the clinical efficacy of BWBDS is significant, the pharmacological mechanism of BWBDS remains unclear. The team performed qualitative and quantitative analysis of BWBDS components with high performance liquid chromatography-tandem mass spectrometry (LC/MS/MS). Network pharmacology was applied to predict possible mechanisms of BWBDS. Cecal ligation and puncture (CLP) was employed to induce sepsis and related injuries caused by post-operative infection. Faecal microbiota transplantation (FMT) and 16S PacBio single-molecule real-time (SMRT) sequencing were used to validate the roles of gut microbiota. Metabolomics analysis was performed to characterise the metabolic profile. Clodronate liposome and anti-interleukin-10 receptor mouse antibody (anti-IL-10R mAb) were used to explore the potential mechanism of bacteria attenuating SILI.

In the study, BWBDS selectively promoted the growth of Lactobacillus in CLP-treated mice. Results of the FMT treatment show that gut bacteria are correlated with sepsis and are required for BWBDS antisepsis effects. The treatment with L. johnsonii significantly prevented mice from sepsis and SILI and improved the survival of mice, which is associated with enhanced gut integrity, as well as reduced intestinal and systemic inflammation. In particular, the research results suggest that the reduction of CLP-induced mortality and alleviation of liver injury by L. johnsonii depend on the promotion of the proportions of IL-10+M2 macrophages. Moreover, the study shows that heat inactivation L. johnsonii (HI-L. johnsonii) treatment can promote the anti-inflammatory activity of macrophages and alleviate SILI.

The team’s findings provide a novel therapeutic approach for SILI. In the foreseeable future, gut microbiota status, such as species diversity, will be used as a biomarker to predict the therapeutic effects of BWBDS in sepsis patients. In addition, BWBDS and the gut bacterium L. johnsonii can be translated to clinical use as novel prebiotics and probiotics for the treatment of sepsis patients. The study has revealed the great potential of TCM in treating sepsis by regulating gut microbiota.

Prof Leung, Prof Xie, and Prof Chen are the co-corresponding authors of the study. PhD students Fan Xiaoqing and Mai Chutian at the Macau University of Science and Technology and PhD student Zuo Ling at the Beijing University of Chinese Medicine are the co-first authors. The project was funded by the Science and Technology Development Fund, Macao SAR (File no: 0096/2018/A3, 0111/2020/A3, 0056/2020/AMJ and 2001/2020/ALC) and UM’s research fund (SRG2022-00020-FHS), and was supported by the 2020 Qi Huang Young Scholar programme of the National Administration of Traditional Chinese Medicine. The full version of the paper can be viewed at https://doi.org/10.1016/j.apsb.2022.10.016.

Source: Faculty of Health Sciences
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