Poria in Fuling Zexie decoction for treating metabolic dysfunction-associated steatotic liver disease: Underlying mechanisms and key bioactive substances

doi:10.4254/wjh.121954

Advanced Search

BPG is committed to discovery and dissemination of knowledge

Home / Archive / Volume 18, Issue 7

This Article

(0)

Peer-Review Report of This Article

CrossCheck and Google Search of This Article

Academic Rules and Norms of This Article

Supplementary Materials of This Article

Citation of this article

Corresponding Author of This Article

Research Domain of This Article

Article-Type of This Article

Open-Access Policy of This Article

Times Cited Counts in Google of This Article

Journal Information of This Article

Publication Name

World Journal of Hepatology

ISSN

1948-5182

Publisher of This Article

Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Hepatol. Jul 27, 2026; 18(7): 121954
Published online Jul 27, 2026. doi: 10.4254/wjh.121954

Poria in Fuling Zexie decoction for treating metabolic dysfunction-associated steatotic liver disease: Underlying mechanisms and key bioactive substances

Yu-Xuan Tao, Di-Hong Gong, Huan Yang, Peng-Quan Wang, Yan-Mei Tang, Qi-Di Zhou, Yan-Yan Wang, Yue Zhang, Wei-Dong Chen, Jie Yu, Xing-Xin Yang

Yu-Xuan Tao, Di-Hong Gong, Huan Yang, Peng-Quan Wang, Yan-Mei Tang, Qi-Di Zhou, Jie Yu, Xing-Xin Yang, College of Pharmaceutical Science, Yunnan University of Chinese Medicine, Yunnan Key Laboratory of Southern Medicine Utilization, Kunming 650500, Yunnan Province, China

Yan-Yan Wang, Yue Zhang, Wei-Dong Chen, School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, Anhui Province, China

Co-first authors: Yu-Xuan Tao and Di-Hong Gong.

Co-corresponding authors: Jie Yu and Xing-Xin Yang.

Author contributions: Tao YX and Gong DH contributed to writing-original draft, methodology, and they contributed equally to this manuscript and are co-first authors; Tao YX contributed to investigation; Tao YX, Tang YM, Zhou QD, Wang YY, Zhang Y, and Yang XX contributed to writing - review and editing; Gong DH and Yang H contributed to visualization; Yang H contributed to formal analysis; Wang PQ contributed to software and data curation; Chen WD, Yu J, and Yang XX contributed to project administration and funding acquisition; Yu J and Yang XX contributed equally to this manuscript and are co-corresponding authors. All authors approved the final manuscript.

AI contribution statement: No AI tools have been used in the preparation, drafting, data analysis, or revision of this manuscript.

Institutional review board statement: All human cell experiments were performed using authenticated commercial cell lines, and no human-derived biological samples were obtained. Our Institutional Ethics Committee granted an institutional review board waiver for this study.

Institutional animal care and use committee statement: Approval was obtained from the Ethical Committee on Animal Care and Experimentation of the Yunnan University of Chinese Medicine (Approval No. R-062023206).

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: All data used to support the findings of this study are available from the corresponding author upon reasonable request.

Corresponding author: Xing-Xin Yang, College of Pharmaceutical Science, Yunnan University of Chinese Medicine, Yunnan Key Laboratory of Southern Medicine Utilization, No. 1076 Yuhua Road, Kunming 650500, Yunnan Province, China. yxx78945@163.com

Received: April 9, 2026
Revised: May 10, 2026
Accepted: June 2, 2026
Published online: July 27, 2026
Processing time: 110 Days and 0.2 Hours

Abstract

BACKGROUND

Fuling Zexie decoction (FZD), in which Poria (PR) occupies the foremost position in the prescription hierarchy, is used to treat metabolic dysfunction-associated steatotic liver disease (MASLD). However, the pharmacodynamic contribution of PR to the effects of FZD remains unclear and the yield of PR from aqueous extraction is limited.

AIM

To clarify the contribution of PR to the effects of FZD in MASLD treatment.

METHODS

The contribution of PR to the therapeutic efficacy of FZD was evaluated in high-fat diet-fed MASLD rats. The mechanisms and active substances were explored by integrating metabolomics and serum pharmacochemistry.

RESULTS

FZD and FZD supplemented with PR dregs alleviated lipid accumulation and tissue fibrosis in MASLD, while FZD without PR (ZD) showed no effect. FZD uniquely altered 148 metabolites and five pathways. FZD exhibited 10 unique drug-derived components in blood, six of which were derived from PR. Moreover, 20 active components in FZD specifically regulated 17 MASLD-related targets, among which the key targets, including phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta, aldo-keto reductase family 1 member B10, and aldo-keto reductase family 1 member B1, were upregulated. Both the key active compounds of FZD and PR-derived compounds in FZD modulated phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha and aldo-keto reductase family 1 member B10 and alleviated cellular steatosis, whereas neither the active compounds of ZD nor those in ZD-derived compounds exhibited such effects.

CONCLUSION

PR, a component of FZD, plays an irreplaceable role in treating MASLD, which may be attributed to the presence of diverse and distinctive components in FZD, along with its specific regulation of five pathways and 148 metabolites. PR residue was shown to enhance the antioxidant and anti-inflammatory effects of FZD.

Keywords: Effective substances; Fuling Zexie decoction; Lipid metabolism; Liver disease; Mechanism; Poria; Metabolic dysfunction-associated steatotic liver disease

Core Tip: This study clarified the specific contribution of Poria (PR) as the “sovereign” drug in Fuling Zexie decoction (FZD) for metabolic dysfunction-associated steatotic liver disease. We confirmed that PR plays an irreplaceable role and its removal significantly weakened the therapeutic efficacy of FZD. The superior effects of FZD were attributed to diverse active components (six derived from PR), the specific regulation of five metabolic pathways (biotin, ascorbate/aldarate, alanine/aspartate/glutamate, inositol phosphate, and galactose metabolism), and 148 differential metabolites. Additionally, incorporating PR dregs enhanced antioxidant and anti-inflammatory activities, indicating that water-insoluble polysaccharides are key bioactive constituents.