Research articles
ScienceAsia 52 (2026): 1-12 |doi:
10.2306/scienceasia1513-1874.2026.037
Hawthorn flavonoids ameliorate NAFLD in mice: Association
with enhanced gut butyrate production and hepatic PI3K/Akt
signaling activation
Wei Chena,?, Li Lib,?, Xueyun Dongc, Hao Xuc, Changhe Zhenga, Bo Zhanga, Wenying Lua, Xin Mad, Na Lie,
Wen Xiaf, Asmaa Alic,g, Liang Wuc,*, Yanxia Chenh,*
ABSTRACT: Gut dysbiosis and disrupted gut-liver crosstalk drive non-alcoholic fatty liver disease (NAFLD), a global
health burden intertwined with obesity and insulin resistance. This study investigated the therapeutic potential
of Hawthorn flavonoid extract (HF) from Crataegus species in NAFLD management, focusing on its modulation
of gut microbiota and metabolic pathways. Using a high-fat diet-induced NAFLD mouse model, 12-week HF
supplementation (100 mg/kg/day) was administered. We evaluated therapeutic effects via hepatic steatosis, systemic
insulin resistance, antioxidant capacity (SOD, GSH-Px, and MDA), and liver histology. Mechanistic insights were
gained through gut microbiota composition, fecal butyrate, hepatic PI3K/Akt activation, and serum metabolomics. HF
significantly attenuated hepatic steatosis, improved insulin sensitivity (p < 0.05), and restored antioxidant capacity by
elevating SOD/GSH-Px activity and suppressing lipid peroxidation (MDA). Histology confirmed reduced hepatic lipid
accumulation and inflammation. Furthermore, HF favorably altered gut microbial composition, enriching beneficial
genera such as Akkermansia and Bacteroides, and increased colonic butyrate production. This microbial shift correlated
with hepatic PI3K/Akt pathway activation (p < 0.05). Serum metabolomics identified HF-mediated reprogramming of
taurine metabolism, glutathione recycling, and glycerophospholipid dynamics. In conclusion, HF alleviates NAFLD
progression by restoring gut microbial ecology, enhancing butyrate production, and activating hepatic PI3K/Akt
signaling, collectively modulating oxidative stress and lipid metabolism.
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| a |
Department of Laboratory Medicine, Yancheng Tinghu District People?s Hospital, Yancheng, Jiangsu 224001 China |
| b |
Department of Clinical Laboratory, Binhai County People?s Hospital, Yancheng, Jiangsu 224500 China |
| c |
Department of Laboratory Medicine, School of Medicine, Jiangsu University, Jiangsu 212013 China |
| d |
Department of Critical Care Medicine, Jurong Hospital, Affiliated to Jiangsu University, Jiangsu 212400 China |
| e |
Department of Clinical Laboratory, Affiliated Women?s Hospital of Jiangnan University, Wuxi 214000 China |
| f |
School of Pharmaceutical and Chemical Technology, Zhenjiang College, Zhenjiang 212028 China |
| g |
Department of Pulmonary Medicine, Abbassia Chest Hospital, EMOH, Cairo 11517 Egypt |
| h |
Department of Orthopedics, Zhenjiang Hospital Affiliated to Nanjing University of Chinese Medicine (Zhenjiang
Hospital of Traditional Chinese Medicine), Zhenjiang 212003 China |
* Corresponding author, E-mail: cyx13861352591@163.com, wl_ujs@163.com
Received 23 Jan 2026, Accepted 31 Mar 2026
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