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image of Salvianolic Acid B-Loaded Albumin Nanoparticles Reduce Portal Hypertension in Cirrhotic Mice and Inhibit the Proliferation and Contraction of Hepatic Stellate Cells

Abstract

Introduction

Salvianolic acid B (SAB), as one of the major water-soluble compounds of , has proved to effectively reduce elevated portal pressure in cirrhotic rats. However, the short half-life and retention time of SAB affect its pharmacodynamics. Therefore, in this study, we prepared albumin nanoparticles loaded with SAB (SAB-ALB-NPs) to improve the retention time of the drug and enhance bioavailability.

Methods

We prepared and characterized SAB-ALB-NPs, including particle size, polydispersity index (PDI), zeta potential, stability, EE, release, and pharmacokinetics. Subsequently, we investigated the effects and potential mechanisms of SAB-ALB-NPs in CCl-induced portal hypertension (PHT) mice models, and it was found that angiotensin-II (Ang-II) induced proliferation and contraction in hepatic stellate cells (HSCs). The CCl (0.3:1 in corn oil, 1mL/kg) was injected repeatedly, leading to the PHT mice model. The effect of SAB-ALB-NPs on PHT mice was evaluated by hematoxylin-eosin, Sirius red staining, immunohistochemistry, and Western blot.

Results

We successfully prepared SAB-loaded albumin nanoparticles with smaller-sized particles, lower PDI and zeta potential with stable properties, and higher EE. Importantly, the SAB-ALB-NPs notably prolonged the release of SAB. SAB-ALB-NPs significantly reduced portal pressure, inhibited inflammation (decrease the concentration of TNF-α and IL-6) and hepatotoxicity of the liver (down-regulated the level of ALT and AST) against fibrous tissue hyperplasia, and reduced collagen deposition in the liver. Afterward, we used Ang-II to facilitate the proliferation of HSCs and induce HSC cell contraction. Cotreatment of SAB-ALB-NPs markedly inhibited Ang II-induced effects on cell proliferation and contraction and improved apoptosis. Importantly, SAB-ALB-NPs were preliminarily found to inhibit the expression of RhoA and ROCK II in Ang-II-treated HSC and CCl-induced PHT mice, suggesting that SAB-ALB-NPs may participate in the regulation of RhoA/ROCK II pathway.

Conclusion

SAB-ALB-NPs improved portal hypertension by suppressing inflammation and inhibiting HSCs activation and proliferation to attenuate liver fibrosis. This therapeutic function of SAB-ALB-NPs may be owing to SAB-ALB-NPs regulating the RhoA/ROCK2 pathway, which may be one of its molecular mechanisms for reducing portal hypertension.

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2025-09-29
2025-10-19

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/content/journals/cpd/10.2174/0113816128364560250124055417
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Salvianolic Acid B-Loaded Albumin Nanoparticles Reduce Portal Hypertension in Cirrhotic Mice and Inhibit the Proliferation and Contraction of Hepatic Stellate Cells
Bentham Science Publishers ; https://doi.org/10.2174/0113816128364560250124055417
/content/journals/cpd/10.2174/0113816128364560250124055417
/content/journals/cpd/10.2174/0113816128364560250124055417
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  • Article Type:     Review Article
Keywords: albumin nanoparticles ; cirrhosis, hepatotoxicity ; portal hypertension ; Salvianolic acid B ; hepatic stellate cells

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