Skip to content
2000
Volume 32, Issue 10
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

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.

© 2026 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpd/10.2174/0113816128364560250124055417
2025-09-29
2026-03-03

  • From This Site

    /content/journals/cpd/10.2174/0113816128364560250124055417
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. KondoR. FurukawaN. DeguchiA. KawataN. SuzukiY. ImaizumiY. YamamuraH. Downregulation of Ca2+-activated Cl- channel TMEM16A mediated by angiotensin II in Cirrhotic portal hypertensive mice.Front. Pharmacol.20221383131110.3389/fphar.2022.83131135370660
     [Google Scholar]
  2. RockeyD.C. Hepatic fibrosis, stellate cells, and portal hypertension.Clin. Liver Dis.200610345947910.1016/j.cld.2006.08.01717162223
     [Google Scholar]
  3. KurikawaN. SugaM. KurodaS. YamadaK. IshikawaH. An angiotensin II type 1 receptor antagonist, olmesartan medoxomil, improves experimental liver fibrosis by suppression of proliferation and collagen synthesis in activated hepatic stellate cells.Br. J. Pharmacol.200313961085109410.1038/sj.bjp.070533912871826
     [Google Scholar]
  4. WuH.T. ChuangY.W. HuangC.P. ChangM.H. Loss of angiotensin converting enzyme II (ACE2) accelerates the development of liver injury induced by thioacetamide.Exp. Anim.2018671414910.1538/expanim.17‑005328845018
     [Google Scholar]
  5. KleinS. Van BeugeM.M. GranzowM. BeljaarsL. SchierwagenR. KilicS. HeidariI. HussS. SauerbruchT. PoelstraK. TrebickaJ. HSC-specific inhibition of Rho-kinase reduces portal pressure in cirrhotic rats without major systemic effects.J. Hepatol.20125761220122710.1016/j.jhep.2012.07.03322878469
     [Google Scholar]
  6. WuY. LiZ. WangS. XiuA. ZhangC. Carvedilol inhibits angiotensin II-induced proliferation and contraction in hepatic stellate cells through the RhoA/Rho-Kinase pathway.BioMed Res. Int.20192019793204610.1155/2019/793204631828132
     [Google Scholar]
  7. XuW. LuC. ZhangF. ShaoJ. YaoS. ZhengS. Dihydroartemisinin counteracts fibrotic portal hypertension via farnesoid X receptor-dependent inhibition of hepatic stellate cell contraction.FEBS J.2017284111413310.1111/febs.1395627896916
     [Google Scholar]
  8. XuH. ZhouY. LuC. PingJ. XuL.M. Salvianolic acid B lowers portal pressure in cirrhotic rats and attenuates contraction of rat hepatic stellate cells by inhibiting RhoA signaling pathway.Lab. Invest.201292121738174810.1038/labinvest.2012.11322986787
     [Google Scholar]
  9. ZhangL. HanL. SunX. GaoD. QinJ. WangJ. The use of PEGylated liposomes to prolong the circulation lifetime of salvianolic acid B.Fitoterapia201283467868910.1016/j.fitote.2012.02.00422391022
     [Google Scholar]
  10. SofiasA.M. DunneM. StormG. AllenC. The battle of “nano” paclitaxel.Adv. Drug Deliv. Rev.2017122203010.1016/j.addr.2017.02.00328257998
     [Google Scholar]
  11. ZhangY. YeZ. HeR. LiY. XiongB. YiM. ChenY. LiuJ. LuB. Bovine serum albumin-based and dual-responsive targeted hollow mesoporous silica nanoparticles for breast cancer therapy.Colloids Surf. B Biointerfaces202322411320110.1016/j.colsurfb.2023.11320136822117
     [Google Scholar]
  12. ChenY. YaoM. PengS. FangY. WanL. ShangW. XiangD. ZhangW. Development of protein-polyphenol particles to stabilize high internal phase Pickering emulsions by polyphenols’ structure.Food Chem.202342813677310.1016/j.foodchem.2023.13677337423104
     [Google Scholar]
  13. ZhaoX. DengB. XuX-Y. YangS-J. ZhangT. SongY-J. LiuX-T. WangY-Q. CaiD-Y. Glycyrrhizinate reduces portal hypertension in isolated perfused rat livers with chronic hepatitis.World J. Gastroenterol.201319366069607610.3748/wjg.v19.i36.606924106408
     [Google Scholar]
  14. SteibC.J. HennenbergM. BeitingerF. HartmannA.C. BystronM. De ToniE.N. GerbesA.L. Amiloride reduces portal hypertension in rat liver cirrhosis.Gut201059682783610.1136/gut.2009.19775620551467
     [Google Scholar]
  15. XuC. DongW. Role of hypoxia-inducible factor-1α in pathogenesis and disease evaluation of ulcerative colitis.Exp. Ther. Med.20161141330133410.3892/etm.2016.303027073444
     [Google Scholar]
  16. XuW. LuC. ZhangF. ShaoJ. ZhengS. Dihydroartemisinin restricts hepatic stellate cell contraction via an FXR-S1PR2-dependent mechanism.IUBMB Life201668537638710.1002/iub.149227027402
     [Google Scholar]
  17. MorenoA.H. BurchellA.R. RousselotL.M. PankeW.F. SlafskyF. BurkeJ.H. Portal blood flow in cirrhosis of the liver.J. Clin. Invest.196746343644510.1172/JCI1055456023778
     [Google Scholar]
  18. WangX. GuH. LiK. LinJ. ZhuY. DengW. DPP4 inhibitor reduces portal hypertension in cirrhotic rats by normalizing arterial hypocontractility.Life Sci.202128411989510.1016/j.lfs.2021.11989534450166
     [Google Scholar]
  19. Pérez TamayoR. Is cirrhosis of the liver experimentally produced by CCl4 and adequate model of human cirrhosis?Hepatology19833111212010.1002/hep.18400301186337081
     [Google Scholar]
  20. BaliA. JaggiA.S. Angiotensin II-triggered kinase signaling cascade in the central nervous system.Rev. Neurosci.201627330131510.1515/revneuro‑2015‑004126574890
     [Google Scholar]
  21. HigashiT. FriedmanS.L. HoshidaY. Hepatic stellate cells as key target in liver fibrosis.Adv. Drug Deliv. Rev.2017121274210.1016/j.addr.2017.05.00728506744
     [Google Scholar]
  22. Gracia-SanchoJ. MarroneG. Fernández-IglesiasA. Hepatic microcirculation and mechanisms of portal hypertension.Nat. Rev. Gastroenterol. Hepatol.201916422123410.1038/s41575‑018‑0097‑330568278
     [Google Scholar]
  23. MakK. Y. ChinR. CunninghamS. C. HabibM. R. TorresiJ. SharlandA. F. AlexanderI. E. AngusP. W. HerathC. B. ACE2 therapy using adeno-associated viral vector inhibits liver fibrosis in mice.Mol Ther201523914341443
     [Google Scholar]
/content/journals/cpd/10.2174/0113816128364560250124055417
Loading
Salvianolic Acid B-Loaded Albumin Nanoparticles Reduce Portal Hypertension in Cirrhotic Mice and Inhibit the Proliferation and Contraction of Hepatic Stellate Cells
Curr. Pharm. Des. 32, 757 (2026); https://doi.org/10.2174/0113816128364560250124055417
/content/journals/cpd/10.2174/0113816128364560250124055417
/content/journals/cpd/10.2174/0113816128364560250124055417
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): albumin nanoparticles; cirrhosis, hepatotoxicity; hepatic stellate cells; portal hypertension; Salvianolic acid B

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test