The Yinzhihuang Oral Liquid (YZH) is a classical Chinese herbal formula used to treat jaundice and acute or chronic liver diseases, with the effects of clearing heat, detoxifying, and promoting liver and gallbladder functions. However, the therapeutic effect of YZH on cyclophosphamide (CTX) -induced liver injury and its underlying mechanisms remain unclear. This study aims to elucidate the relevant mechanisms of YZH in treating CTX-induced murine liver injury through multi-omics techniques. A total of 24 male ICR mice were randomly assigned to four groups: control (CON), model (MOD), positive control (silibinin, SIL), and drug treatment (YZH), with six mice per group. A mouse model of liver injury was induced via intraperitoneal injection of CTX at 80 mg/kg. Five days after modeling, the MOD, SIL, and YZH groups were administered normal saline, SIL, or YZH, respectively, at equivalent volumes. All mice were euthanized 12 days after the initial injection. The therapeutic efficacy of YZH was assessed based on serum biochemical parameters, histopathological evaluation, and immunofluorescence analysis. Furthermore, the underlying mechanisms of YZH were investigated using multi-omics approaches. YZH administration significantly ameliorated CTX-induced liver injury, including restoring the expression levels of tight junction proteins (TJs), increasing the activities of antioxidant enzymes, and suppressing the release of downstream inflammatory factors. Gut microbiota analysis indicated that YZH notably enhanced the abundance and diversity of intestinal microbiota, and increased the relative abundance of beneficial bacteria (norankf_Muribaculaceae, Bacteroides, Parabacteroides, Alistipes, Rikenella, Odoribacter, PrevotellaceaeUCG-001, and Alloprevotella). Fecal metabolomic analysis revealed that YZH could modulate glycerophospholipid metabolism, pyrimidine metabolism, and histidine metabolism to alleviate the CTX-induced liver injury. Spearman’s analysis demonstrated a strong correlation between gut microbiota composition and fecal metabolite levels. This study suggests that YZH exerts crucial roles in a comprehensive treatment approach for CTX-induced liver injury, possibly by enhancing intestinal barrier function, improving gut microbiota dysbiosis, and regulating metabolic disorders to alleviate hepatic inflammation.
Zhang et al. (Wed,) studied this question.
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