Lonicerin from Dachaihu decoction ameliorates liver steatosis and fibrosis in MASH by inhibiting LY6D
- J Ethnopharmacol. 2026 Jun 22:371:122097. doi: 10.1016/j.jep.2026.122097.
- 1. Affiliated Jiangning Chinese Medicine Hospital, China Pharmaceutical University, Nanjing, 211100, PR China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, PR China.
- 2. Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Guangxi Institute of Chinese Medicine & Pharmaceutical Science, PR China.
- 3. School of Pharmacy, Air Force Medical University, Xi'an, 710032, PR China.
- 4. School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, PR China.
- 5. Affiliated Jiangning Chinese Medicine Hospital, China Pharmaceutical University, Nanjing, 211100, PR China.
- 6. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, PR China.
- 7. Affiliated Jiangning Chinese Medicine Hospital, China Pharmaceutical University, Nanjing, 211100, PR China; School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, PR China. Electronic address: [email protected].
- 8. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, PR China; School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, PR China. Electronic address: [email protected].
Ethnopharmacological relevance: Dachaihu Decoction (DCHD) is a traditional Chinese medicine formula from the Shanghan Lun. It has been used for over 1800 years to treat "Shaoyang and Yangming concurrent syndromes", which are closely related to modern liver disorders, including metabolic dysfunction-associated steatohepatitis (MASH). While DCHD has demonstrated hepatoprotective effects in preclinical studies, the specific bioactive components and mechanism of action against MASH remain elusive.
Aim of the study: To systematically identify the key active components of DCHD mediating its anti-MASH effects and to elucidate their molecular mechanisms.
Materials and methods: The components in DCHD were characterized using high resolution-mass spectrometry (HRMS). The potential bioactive components were screened using network pharmacology. The therapeutic efficacy of candidate compounds was evaluated both in free fatty acid (FFA)-induced hepatocyte injury and activated hepatic stellate cells (HSCs) and in a high-fat diet/CCl4-induced MASH mouse model. The molecular mechanism was investigated via transcriptomic profiling, drug-target interaction validation, and gene knockdown assays.
Results: A total of 128 components were identified from DCHD using HRMS. Lonicerin (LON), a flavonoid glycoside predominantly derived from Citrus trifoliata L., was identified as the key active component. LON significantly ameliorated steatosis, inflammation and fibrosis both in vitro and in vivo. Mechanistically, LON bound to lymphocyte antigen 6 family member D (LY6D), which was significantly upregulated during MASH progression, and dose-dependently suppressed its expression. Importantly, LY6D knockdown abolished the protective effect of LON in AML12 hepatocytes and activated HSCs, confirming LY6D as a functional target.
Conclusions: This study identified LON as a key bioactive component mediating the anti-MASH effects of DCHD and revealed that it alleviated MASH progression by targeting LY6D.