Multi-omics Profiling Reveals the Effects of Xihuangcao on Hepatic Fibrosis Attenuation through Gut Microbiota and Metabolic Reprogramming.
7 affiliations
- 1Department of Pharmacy, Zhongshan City People's Hospital, Zhongshan 528403, China.
- 2Center for Drug Research and Development, Guangdong Provincial Key Laboratory of Advanced Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou 510006, China.
- 3Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou 510006, China.
- 4Department of Gastroenterology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510080, China.
- 5The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, China.
- 6Hutchison Whampoa Guangzhou Baiyunshan, Chinese Medicine Company Limited, Guangzhou 510006, China.
- 7Consun Pharmaceutical Group Limited, Guangzhou, Guangdong 510006, China.
Abstract
In various chronic liver diseases, hepatic fibrosis represents a frequent pathological event. This process involves the activation of hepatic stellate cells, along with the consequent excessive deposition of extracellular matrix. Emerging evidence highlights the contribution of gut microbiota dysbiosis and intestinal barrier dysfunction to its progression, underscoring the potential of targeting the liver-gut axis. Xihuangcao, a traditional Chinese medicinal herb used for acute cholecystitis and jaundice hepatitis, exhibits antifibrotic activity, but its underlying mechanisms remain unclear. In this study, hepatic fibrosis models were established to evaluate the antifibrotic effects of 3 botanical sources of Xihuangcao (Isodon lophanthoides (Buch.-Ham. ex D.Don) H.Hara, Isodon lophanthoides var. graciliflorus (Benth.) H.Hara, and Isodon serra Kudô) through integrating histopathological, transcriptomics, metabolomics, 16S ribosomal RNA (rRNA) sequencing, and network pharmacology analyses. The results indicated that all 3 botanical sources of Xihuangcao markedly alleviated hepatic fibrosis and reduced collagen deposition. Transcriptomic analysis revealed that Xihuangcao down-regulated profibrotic mediators (Toll-like receptor 5, transforming growth factor-β, and platelet-derived growth factor) and modulated mitogen-activated protein kinase, steroid biosynthesis, bile secretion, and retinol metabolism pathways, highlighting its coordinated suppression of inflammation-driven fibrogenic activation in hepatic fibrosis. Liver metabolomics revealed Xihuangcao's effect on restoration of energy metabolism, amino acid turnover, and redox homeostasis. Xihuangcao also corrected fibrosis-induced gut dysbiosis, characterized by reduced Verrucomicrobia and increased S24-7 abundance, while suppressing pathogenic genera such as Clostridium and Prevotella. Moreover, Xihuangcao decreased profibrotic metabolites (androstan-3α,17β-diol) and suppressed choline-related metabolic pathways associated with fibrogenic signaling. Network pharmacology and experimental validation further identified PI3K/Akt inhibition as a key mechanism suppressing hepatic stellate cell activation. In summary, this study, based on integrative multi-omics analyses (metabolomics, transcriptomics, and 16S rRNA sequencing), found that Xihuangcao alleviates liver fibrosis by modulating inflammatory responses, metabolic disorders, and gut microbiota dysbiosis via the gut-liver axis. Furthermore, network pharmacology combined with in vitro experiments revealed that inhibition of hepatic stellate cell activation through the PI3K/Akt pathway may be the critical mechanism underlying its therapeutic efficacy.
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BibTeX
@article{zhao2026multiomics,
title = {{Multi-omics Profiling Reveals the Effects of Xihuangcao on Hepatic Fibrosis Attenuation through Gut Microbiota and Metabolic Reprogramming.}},
author = {Weiguo Zhao and Xueling Zhang and Lifan Xu and Mianfeng Zheng and Zhuoya Li and Yuexuan Wang and Xinxiang He and Min Hong and Huiye Zhang and Junwei Li and Lei Shi and Ying Du and Haitao Yuan and Wei Zhang and Ali Chen},
journal = {Biomaterials research},
year = {2026},
month = oct,
doi = {10.34133/bmr.0422},
url = {https://europepmc.org/article/MED/42898675},
note = {CC BY},
}
RIS
TY - JOUR
TI - Multi-omics Profiling Reveals the Effects of Xihuangcao on Hepatic Fibrosis Attenuation through Gut Microbiota and Metabolic Reprogramming.
AU - Weiguo Zhao
AU - Xueling Zhang
AU - Lifan Xu
AU - Mianfeng Zheng
AU - Zhuoya Li
AU - Yuexuan Wang
AU - Xinxiang He
AU - Min Hong
AU - Huiye Zhang
AU - Junwei Li
AU - Lei Shi
AU - Ying Du
AU - Haitao Yuan
AU - Wei Zhang
AU - Ali Chen
PY - 2026
DA - 2026/10/19
JO - Biomaterials research
DO - 10.34133/bmr.0422
UR - https://europepmc.org/article/MED/42898675
AB - In various chronic liver diseases, hepatic fibrosis represents a frequent pathological event. This process involves the activation of hepatic stellate cells, along with the consequent excessive deposition of extracellular matrix. Emerging evidence highlights the contribution of gut microbiota dysbiosis and intestinal barrier dysfunction to its progression, underscoring the potential of targeting the liver-gut axis. Xihuangcao, a traditional Chinese medicinal herb used for acute cholecystitis and jaundice hepatitis, exhibits antifibrotic activity, but its underlying mechanisms remain unclear. In this study, hepatic fibrosis models were established to evaluate the antifibrotic effects of 3 botanical sources of Xihuangcao (Isodon lophanthoides (Buch.-Ham. ex D.Don) H.Hara, Isodon lophanthoides var. graciliflorus (Benth.) H.Hara, and Isodon serra Kudô) through integrating histopathological, transcriptomics, metabolomics, 16S ribosomal RNA (rRNA) sequencing, and network pharmacology analyses. The results indicated that all 3 botanical sources of Xihuangcao markedly alleviated hepatic fibrosis and reduced collagen deposition. Transcriptomic analysis revealed that Xihuangcao down-regulated profibrotic mediators (Toll-like receptor 5, transforming growth factor-β, and platelet-derived growth factor) and modulated mitogen-activated protein kinase, steroid biosynthesis, bile secretion, and retinol metabolism pathways, highlighting its coordinated suppression of inflammation-driven fibrogenic activation in hepatic fibrosis. Liver metabolomics revealed Xihuangcao's effect on restoration of energy metabolism, amino acid turnover, and redox homeostasis. Xihuangcao also corrected fibrosis-induced gut dysbiosis, characterized by reduced Verrucomicrobia and increased S24-7 abundance, while suppressing pathogenic genera such as Clostridium and Prevotella. Moreover, Xihuangcao decreased profibrotic metabolites (androstan-3α,17β-diol) and suppressed choline-related metabolic pathways associated with fibrogenic signaling. Network pharmacology and experimental validation further identified PI3K/Akt inhibition as a key mechanism suppressing hepatic stellate cell activation. In summary, this study, based on integrative multi-omics analyses (metabolomics, transcriptomics, and 16S rRNA sequencing), found that Xihuangcao alleviates liver fibrosis by modulating inflammatory responses, metabolic disorders, and gut microbiota dysbiosis via the gut-liver axis. Furthermore, network pharmacology combined with in vitro experiments revealed that inhibition of hepatic stellate cell activation through the PI3K/Akt pathway may be the critical mechanism underlying its therapeutic efficacy.
SN - 1226-4601
SN - 2055-7124
ER -