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Lianhe Xiaozhi ointment ameliorates metabolic dysfunction-associated steatotic liver disease via peroxisome proliferator-activated receptor alpha pathway activation
Xi-Qiao Zhou, Jiang-Yi Yu, Yi-Fan Lu, Yan Lou, Yu-Tian Cao, Jing Sun, Xin-Yi Yang, Gao-Xiang Wang, Li-Juan Nie
Li-Juan Nie, Gao-Xiang Wang, Xin-Yi Yang, Jing Sun, Yu-Tian Cao, Yan Lou, Yi-Fan Lu, Jiang-Yi Yu, Xi-Qiao Zhou, Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
Li-Juan Nie, Department of Science and Education, Affiliated Psychological Hospital of Anhui Medical University, Hefei Fourth People’s Hospital, Hefei 230022, Anhui Province, China
Xin-Yi Yang, Jing Sun, Yu-Tian Cao, The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Co-first authors: Li-Juan Nie and Gao-Xiang Wang.
Author contributions: Zhou XQ and Nie LJ conceived the idea and designed the study; Nie LJ, Wang GX, Yang XY and Zhou XQ wrote the study protocol; Nie LJ, Wang GX, Yang XY, Sun J, Cao YT, Lou Y, Lu YF, Yu JY and Zhou XQ participated in the discussion and modification of the experimental plan; Nie LJ, Wang GX, and Yang XY performed the research and data analyses; Nie LJ wrote the manuscript; Zhou XQ revised the manuscript; all authors had approved the final manuscript for submission.
Supported by the National Natural Science Foundation of China, No. 82474318; the Jiangsu Administration of Traditional Chinese Medicine, No. QN202411; and the Special Fund for Training Outstanding Young Doctors in the Second Session of Jiangsu Province Hospital of Chinese Medicine, No. 2024QB002.
Institutional review board statement: The study does not involve any human experiments.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of of Nanjing University of Chinese Medicine (No. 202212A024).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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: Detailed methods and datasets that support the findings of the present study are available from the corresponding author upon reasonable request.
Corresponding author: Xi-Qiao Zhou, PhD, Professor, Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, No. 155 Hanzhong Road, Qinhuai District, Nanjing 210029, Jiangsu Province, China.
zhouxiqiao@njucm.edu.cn
Received: September 30, 2025
Revised: November 6, 2025
Accepted: December 25, 2025
Published online: March 7, 2026
Processing time: 151 Days and 5.3 Hours
BACKGROUND
Lianhe Xiaozhi ointment (LXO), an innovative formulation derived from the classic Huanglian Wendan decoction, has been granted a national invention patent. With increasing years of clinical expertise within the Jiangsu Province Hospital of Chinese Medicine in China, LXO has become increasingly recognized as a potent remedy for metabolic disorders, particularly metabolic dysfunction-associated steatotic liver disease (MASLD). To date, specific bioactive components and underlying mechanisms remain unclear.
AIM
To determine the bioactive components of LXO and clarify its mechanisms of action relevant to management of MASLD.
METHODS
We used ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and network pharmacology approaches to systematically determine the key bioactive components of LXO and elucidate biological pathways modulated in the treatment of MASLD. Critical signaling pathways were also elucidated via hepatic transcriptomic analysis, and an exhaustive and rigorous exploration of the therapeutic efficacy and underlying mechanisms of LXO in MASLD was conducted via a combination of in vivo and in vitro high-fat model experiments.
RESULTS
Network pharmacology analysis revealed six pivotal bioactive components within LXO that collectively serve as the cornerstone for their efficacy against MASLD. LXO exerts multiple therapeutic effects, including weight gain retardation, amelioration of glucose and lipid metabolism disturbances, liver injury mitigation, hepatic inflammation alleviation, and correction of gut microbiota disorders. Multiple platform analyses, including hepatic transcriptomics, quantitative real-time polymerase chain reaction, and western blotting, confirmed that LXO induces peroxisome proliferator-activated receptor alpha (PPARα) transcriptional activation in the liver. In vitro studies confirmed that a PPARα antagonist markedly diminishes the lipid-lowering capacity of LXO.
CONCLUSION
Collectively, our findings suggest that LXO exerts therapeutic effects on high-fat diet-induced MASLD at least in part via PPARα pathway activation.
Core Tip: Lianhe Xiaozhi ointment effectively alleviates metabolic dysfunction-associated steatotic liver disease by improving glucolipid metabolism, reducing liver injury and inflammation, and modulating gut microbiota. Its therapeutic effect is primarily mediated via activation of peroxisome proliferator-activated receptor alpha signaling. These insights provide a theoretical foundation for the clinical application of Lianhe Xiaozhi ointment.
