Catalpol relieved angiotensin II-induced blood-brain barrier destruction via inhibiting the TLR4 pathway in brain endothelial cells.
Pharm Biol
; 60(1): 2210-2218, 2022 Dec.
Article
em En
| MEDLINE
| ID: mdl-36369944
ABSTRACT
CONTEXT Catalpol is a major bioactive constituent of Rehmannia glutinosa Libosch (Scrophulariaceae), a traditional Chinese medicine, which is widely used in multiple diseases, including hypertension. OBJECTIVES:
To explore whether catalpol protects against angiotensin II (Ang II)-triggered blood-brain barrier (BBB) leakage. MATERIALS ANDMETHODS:
The bEnd.3 cells and BBB models were pre-treated with or without catalpol (50, 200 and 500 µM) or TAK-242 (1 µM) for 2 h and then with Ang II (0.1 µM) or LPS (1 µg/mL) for 24 h. Cell viability was determined by the MTT assay. The levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), inducible nitric oxide synthase (iNOS), tumour necrosis factor-α (TNF-α), caveolin-1 (Cav-1) and p-eNOS/eNOS were tested by western blot. The BBB permeability was evaluated by the flux of bovine serum albumin-fluorescein isothiocyanate (BSA-FITC) across monolayers. nuclear factor kappa-B (NF-κB) p65 nuclear translocation was explored by immunofluorescence staining.RESULTS:
Ang II (0.1 µM) decreased the cell viability to 86.52 ± 1.79%, elevated the levels of TLR4, MyD88, iNOS, TNF-α and Cav-1 respectively to 3.7-, 1.5-, 2.3-, 2.2- and 2.7-fold, reduced the level of p-eNOS/eNOS to 1.6-fold in bEnd.3 cells, and eventually increased BBB permeability. Catalpol dose-dependently reversed these changes at 50-500 µM. Meanwhile, catalpol (500 µM) inhibited the upregulated levels of TLR4 pathway-related proteins and NF-κB p65 nuclear translocation, decreased the enhanced transcytosis, and relieved the BBB disruption caused by both LPS (the TLR4 activator) and Ang II. The effects are same as TAK-242 (the TLR4 inhibitor).CONCLUSIONS:
Catalpol relieved the Ang II-induced BBB damage, which indicated catalpol has high potential for the treatment of hypertension-induced cerebral small vessel disease (cSVD).Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Medicinas Tradicionais:
Medicinas_tradicionales_de_asia
/
Medicina_china
Assunto principal:
Barreira Hematoencefálica
/
Células Endoteliais
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Pharm Biol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China