Discovery of adamantane-type polycyclic polyprenylated acylphloroglucinols that can prevent concanavalin A-induced autoimmune hepatitis in mice.
Bioorg Chem
; 144: 107145, 2024 Mar.
Article
in En
| MEDLINE
| ID: mdl-38278050
ABSTRACT
Hyperadamans A-G (1-7), seven new adamantane type polycyclic polyprenylated acylphloroglucinols (PPAPs), were isolated from Hypericum wilsonii N. Robson. Structurally, 1-4 were the first adamantanes bearing an unusual 2,7-dioxabicyclo-[2.2.1]-heptane fragment, and compound 5 was the first adamantane with a rare 1,6-dioxaspiro[4.4]nonane section. Importantly, 1-7 exhibited significant immunosuppressive activity on Con A-induced T-lymphocyte proliferation in vitro, with IC50 values ranging from 3.97 ± 0.10 to 18.12 ± 1.07 µM. Pretreatment with 1 in Con A-challenged autoimmune hepatitis mice could dramatically ameliorate the levels of hepatic injury indexes (ALT and AST) and reduce the product of proinflammatory cytokines (COX-2, IL-6, IL-1ß, IL-18, IL-23A and TNF-α). Furthermore, the protective effect of 1 on the Con A-induced liver injury was corroborated by the histological analysis and the immunohistochemistry.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adamantane
/
Hepatitis, Autoimmune
Limits:
Animals
Language:
En
Journal:
Bioorg Chem
/
Bioorganic chem
/
Bioorganic chemistry
Year:
2024
Document type:
Article
Country of publication:
Estados Unidos