Nanodrug rescues liver fibrosis via synergistic therapy with H2O2 depletion and Saikosaponin b1 sustained release
Open accessAbstract
Hypoxia and hydrogen peroxide (H 2 O 2) accumulation form the profibrogenic liver environment, which involves fibrogenesis and chronic stimulation of hepatic stellate cells (HSCs). Catalase (CAT) is the major antioxidant enzyme that catalyzes H 2 O 2 into oxygen and water, which loses its activity in different liver diseases, especially in liver fibrosis. Clinical specimens of cirrhosis patients and liver fibrotic mice are collected in this work, and results show that CAT decrease is closely correlated with hypoxia-induced transforminmg growth factor β1 (TGF-β1). A multifunctional nanosystem combining CAT-like MnO 2 and anti-fibrosis Saikosaponin b1 (Ssb1) is subsequently constructed for antifibrotic therapy. MnO 2 catalyzes the accumulated H 2 O 2 into oxygen, thereby ameliorating the hypoxic and oxidative stress to prevent activation of HSCs, and assists to enhance the antifibrotic pharmaceutical effect of Ssb1. This work suggests that TGF-β1 is responsible for the diminished CAT in liver fibrosis, and our designed MnO 2@PLGA/Ssb1 nanosystem displays enhanced antifibrotic efficiency through removing excess H 2 O 2 and hypoxic stress, which may be a promising therapeutic approach for liver fibrosis treatment.
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Ssb1 can effectively drive the apoptosis of aHSCs and the degradation of ECM in CCl4-induced fibrotic models, thereby protecting mice against liver fibrosis.
“Our previous study demonstrated that Ssb1 can effectively drive the apoptosis of aHSCs and the degradation of ECM in CCl4‐induced fibrotic models, therefore protecting mice against liver fibrosis [17].”
From Saikosaponin b1 Attenuates Liver Fibrosis by Blocking STAT3/Gli1 Interaction and Inducing Gli1 Degradation (2025) · cites this paper as [17]
The Results section on cellular antifibrotic efficiency reports that Ssb1 induced apoptosis in activated HSCs. The mouse Results report reduced collagen-gene expression after Ssb1 treatment, but do not establish ECM degradation. The Discussion says Ssb1 alone was minimally effective at reversing fibrosis in CCl4-treated mice; the more effective treatment combined Ssb1 with MnO2. (LLM, conf=0.89)
Experimental — accuracy not yet measuredSsb1 is a promising antifibrosis compound effective in inducing aHSC apoptosis.
“Our previous study showed that Ssb1 is a promising antifibrosis compound that is effective in inducing aHSC apoptosis [17].”
From Saikosaponin b1 Attenuates Liver Fibrosis by Blocking STAT3/Gli1 Interaction and Inducing Gli1 Degradation (2025) · cites this paper as [17]
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- Authors
- Peng, M., Shao, M., Dong, H., Han, X., Hao, M., Yang, Q., Lyu, Q., Tang, D., Shen, Z., Wang, K., Kuang, H., & Cao, G.
- Affiliations
- Zhejiang Chinese Medical University (CN)
- Guiyang University (CN)
- First Affiliated Hospital Zhejiang University (CN)
- Corresponding author
- Cao, Gang
- Venue
- Communications Biology
- Published
- 2023-02-16
- Volume
- 6
- Issue
- 1
- Pages
- 184-184
- ISSN
- 2399-3642 (ISSN-L)
- PMC
- PMC9935535
- OpenAlex
- W4321018197
- Cited by
- 22
- References
- 61
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 5 · 2023: 3
- FWCI
- 3.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Communications Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (52003246, 81922073, 81973481)
- Chinese Medicine Research Program of Zhejiang Province (2022ZQ032, 2018ZY004, 2021ZZ009)
- Zhejiang Chinese Medical University (2021JKZKTS007A)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Physical Sciences › Materials Science › Materials Chemistry › Advanced Nanomaterials in Catalysis
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- liver fibrosis, hepatic stellate cell activation, TGF-β1, hypoxia, oxidative stress, sustained drug release, antifibrotic therapy, nanotherapeutics
- MeSH terms
- Animals, Delayed-Action Preparations, Humans, Hydrogen Peroxide, Liver Cirrhosis, Oleanolic Acid, Oxides, Oxygen, Saponins, Manganese Compounds, Mice, Nanoparticles, Transforming Growth Factor beta1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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