Luteolin-loaded exosomes derived from bone marrow mesenchymal stem cells: a promising therapy for liver fibrosis
Open accessAbstract
Liver fibrosis is a global life-threatening disorder with no approved treatment. It leads to serious hepatic complications when progressive, such as cirrhosis and carcinoma. Luteolin (LUT) is a plant flavonoid possessing a promising therapeutic potential in various liver diseases particularly, liver fibrosis. It was reported to have potent anti-inflammatory and antioxidant properties. It also suppresses the proliferation of activated hepatic stellate cells (HSC) and induces their apoptosis. However, its poor aqueous solubility and exposure to metabolism hinder its clinical use. Mesenchymal stem cells (MSCs)-derived exosomes, nano-sized extracellular vesicles, have recently emerged as natural biocompatible drug delivery vehicles permitting efficient drug delivery. Accordingly, the present study aimed for the first time to investigate the potential of bone marrow MSCs-derived exosomes to improve LUTs antifibrotic effectiveness. LUT-loaded exosomes (LUT-Ex) were successfully developed, optimized and subjected to both in vitro and in vivo characterization. The elaborated LUT-Ex presented good colloidal properties (size; 150 nm, PDI; 0.3 and ζ-potential; −28 mV), typical vesicular shape, reasonable drug entrapment efficiency (40%) with sustained drug release over 72 h. Additionally, the cellular uptake study of coumarin-6-loaded exosomes in HEP-G2 revealed a significant enhancement in their uptake by 78.4% versus free coumarin-6 solution (p ≤ 0.001). Following a single intraperitoneal injection, LUT-Ex revealed a superior antifibrotic activity compared with either LUT-suspension or blank exosomes as evidenced by the results of biochemical and histopathological evaluation. In conclusion, the elaborated LUT-Ex could be addressed as a promising nanocarrier for effective treatment of liver fibrosis.
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MSC-Exos loaded with obeticholic acid or luteolin exhibited superior anti-fibrotic effects compared with either drugs or MSC-Exos alone.
“It has been reported that MSC-Exos loaded with obeticholic acid or luteolin exhibited superior anti-fibrotic effects compared with either drugs or MSC-Exos alone [266, 267].”
From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [267]
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Regenerating Earthworm-Derived Extracellular Vesicles Enhance Mouse Fibroblast Growth and Migration
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Biology and Therapeutic Potential of Exosomes, Targeted Drug Delivery
Mateos-Ramírez, F. A. G., Hernández‐Ortega, L. D., Gurrola‐Díaz, C. M., Gasca-Lozano, L. E., Sánchez-Orozco, L. V., & Salazar-Montes, A. M. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27188145
- Authors
- Ashour, A. A., El-Kamel, A. H., Mehanna, R. A., Mourad, G., & Heikal, L. A.
- Affiliations
- Alexandria University (EG)
- Corresponding author
- El-Kamel, Amal H.
- Venue
- Drug Delivery
- Publisher
- Informa UK Limited
- Published
- 2022-11-03
- Volume
- 29
- Issue
- 1
- Pages
- 3270-3280
- ISSN
- 1071-7544 (ISSN-L)
- 1521-0464
- PMC
- PMC9639476
- OpenAlex
- W4308631125
- Cited by
- 60
- References
- 42
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 22 · 2023: 11
- FWCI
- 4.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Drug Delivery (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Greater South Information System
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- luteolin, exosomes, bone marrow mesenchymal stem cells, liver fibrosis, extracellular vesicles, coumarin 6, hepatic stellate cells, antifibrotic activity, encapsulation efficiency, sustained drug release, cellular uptake, flavonoids
- MeSH terms
- Coumarins, Humans, Liver Cirrhosis, Luteolin, Exosomes, Mesenchymal Stem Cells
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