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Peer-reviewedCC BY 4.0Molecules

Oleanolic Acid-Loaded Cyclodextrin Metal–Organic Framework Ameliorates NAFLD via Modulation of Gut Microbiota and Liver Metabolism

  • Hua Zhu1
  • Minmin Tang2
  • Meng Li3
  • Zhenhua Zhang1
  • Liqin Kang1
  • Qiaona Wang4
  • Renlei Wang1
  • Chun Hua5
  • Huiming Zhou5
  • Wenzhi Zhou6
  • Yinliang Wu6
  • Zhenjiong Wang3
6 affiliations
  1. 1Key Laboratory of Innovative Applications of Bioresources and Functional Molecules of Jiangsu Province, College of Life Science and Chemistry, Jiangsu Second Normal University, Nanjing 211200, China
  2. 2Key Laboratory of Food Contact Materials Safety, State Administration for Market Regulation, Jiangsu Product Quality Testing & Inspection Institute, Nanjing 210007, China
  3. 3Collaborative Innovation Center for Modern Grain Circulation and Safety, College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing 210023, China
  4. 4School of Ecology and Applied Meteorology, Nanjing University of Information Science & Technology, Nanjing 210044, China
  5. 5School of Food Science, Nanjing Xiaozhuang University, Nanjing 211171, China
  6. 6Jiangsu Sanshu Biotechnology Go., Ltd., No. 259 Shibei Gaoxin Road, Chongchuan District, Nantong 226001, China
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Abstract

Oleanolic acid (OA) possesses hepatoprotective properties, but its clinical application is hampered by poor aqueous solubility. This study aimed to enhance OA solubility and investigate its therapeutic mechanism for NAFLD by encapsulating it in a γ-cyclodextrin metal–organic framework (OA@CDMOF). The OA@CDMOF complex was synthesized and characterized. Its effects on a high-fat diet (HFD)-induced NAFLD mouse model (MOD) were evaluated by combined liver metabolomics and 16S rRNA amplicon sequencing analyses. When encapsulated into CDMOF to yield an OA@CDMOF complex, the solubility of OA significantly improved. OA@CDMOF administration ameliorated HFD-induced metabolic alterations and liver injury. It modulated the gut microbiota composition, notably enriching the phylum Firmicutes while decreasing the abundance of Bacteroidota. Liver metabolomic analysis revealed that OA@CDMOF was associated with changes in metabolites related to glycerophospholipid, purine, glutathione, and vitamin B6 metabolism. Furthermore, it was associated with changes in metabolites related to lipolysis in adipocytes, pentose and glucuronate interconversions, and key signaling pathways, including AMPK, FoxO, and cGMP-PKG. Importantly, OA@CDMOF showed protective effects comparable to those of free OA, with no statistically significant difference between the two groups. This study elucidates the mechanism by which OA@CDMOF alleviates NAFLD through modulation of the gut microbiome and host metabolism. Our findings provide novel insights into the hepatoprotective role of OA@CDMOF and suggest a promising nanostrategy for NAFLD intervention.

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Cite

BibTeXRIS
BibTeX
@article{zhu2026oleanolic,
  title = {{Oleanolic Acid-Loaded Cyclodextrin Metal–Organic Framework Ameliorates NAFLD via Modulation of Gut Microbiota and Liver Metabolism}},
  author = {Hua Zhu and Minmin Tang and Meng Li and Zhenhua Zhang and Liqin Kang and Qiaona Wang and Renlei Wang and Chun Hua and Huiming Zhou and Wenzhi Zhou and Yinliang Wu and Zhenjiong Wang},
  journal = {Molecules},
  year = {2026},
  month = oct,
  doi = {10.3390/molecules31203663},
  url = {https://www.mdpi.com/1420-3049/31/20/3663},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Oleanolic Acid-Loaded Cyclodextrin Metal–Organic Framework Ameliorates NAFLD via Modulation of Gut Microbiota and Liver Metabolism
AU  - Hua Zhu
AU  - Minmin Tang
AU  - Meng Li
AU  - Zhenhua Zhang
AU  - Liqin Kang
AU  - Qiaona Wang
AU  - Renlei Wang
AU  - Chun Hua
AU  - Huiming Zhou
AU  - Wenzhi Zhou
AU  - Yinliang Wu
AU  - Zhenjiong Wang
PY  - 2026
DA  - 2026/10/01
JO  - Molecules
DO  - 10.3390/molecules31203663
UR  - https://www.mdpi.com/1420-3049/31/20/3663
AB  - Oleanolic acid (OA) possesses hepatoprotective properties, but its clinical application is hampered by poor aqueous solubility. This study aimed to enhance OA solubility and investigate its therapeutic mechanism for NAFLD by encapsulating it in a γ-cyclodextrin metal–organic framework (OA@CDMOF). The OA@CDMOF complex was synthesized and characterized. Its effects on a high-fat diet (HFD)-induced NAFLD mouse model (MOD) were evaluated by combined liver metabolomics and 16S rRNA amplicon sequencing analyses. When encapsulated into CDMOF to yield an OA@CDMOF complex, the solubility of OA significantly improved. OA@CDMOF administration ameliorated HFD-induced metabolic alterations and liver injury. It modulated the gut microbiota composition, notably enriching the phylum Firmicutes while decreasing the abundance of Bacteroidota. Liver metabolomic analysis revealed that OA@CDMOF was associated with changes in metabolites related to glycerophospholipid, purine, glutathione, and vitamin B6 metabolism. Furthermore, it was associated with changes in metabolites related to lipolysis in adipocytes, pentose and glucuronate interconversions, and key signaling pathways, including AMPK, FoxO, and cGMP-PKG. Importantly, OA@CDMOF showed protective effects comparable to those of free OA, with no statistically significant difference between the two groups. This study elucidates the mechanism by which OA@CDMOF alleviates NAFLD through modulation of the gut microbiome and host metabolism. Our findings provide novel insights into the hepatoprotective role of OA@CDMOF and suggest a promising nanostrategy for NAFLD intervention.
SN  - 1420-3049
ER  -