1,8-cineole ameliorates colon injury by downregulating macrophage M1 polarization via inhibiting the HSP90-NLRP3-SGT1 complex
10.1016/j.jpha.2023.07.001
- Author:
Shengsuo MA
1
,
2
;
Bing YANG
;
Yang DU
;
Yiwen LV
;
Jiarong LIU
;
Yucong SHI
;
Ting HUANG
;
Huachong XU
;
Li DENG
;
Xiaoyin CHEN
Author Information
1. School of Traditional Chinese Medicine,Jinan University,Guangzhou,510632,China
2. Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine,Jinan University,Guangzhou,510632,China
- Keywords:
1,8-cineole;
Amomum compactum Sol.ex Maton;
NLRP3;
HSP90;
Ulcerative colitis;
Intestinal barrier function
- From:
Journal of Pharmaceutical Analysis
2023;13(9):984-998
- CountryChina
- Language:Chinese
-
Abstract:
Ulcerative colitis(UC)is characterized by chronic relapsing intestinal inflammation.Currently,there is no effective treatment for the disease.According to our preliminary data,1,8-cineole,which is the main active compound of Amomum compactum Sol.ex Maton volatile oil and an effective drug for the treat-ment of pneumonia,showed remarkable anti-inflammatory effects on colitis pathogenesis.However,its mechanism of action and direct targets remain unclear.This study investigated the direct targets and mechanism through which 1,8-cineole exerts its anti-inflammatory effects using a dextran sulfate so-dium salt-induced colitis mouse model.The effects of 1,8-cineole on macrophage polarization were investigated using activated bone marrow-derived macrophages and RAW264.7 cells.In addition,1,8-cineole targets were revealed by drug affinity responsive target stability,thermal shift assay,cellular thermal shift assay,and heat shock protein 90(HSP90)adenosine triphosphatases(ATPase)activity assays.The results showed that 1,8-cineole exhibited powerful anti-inflammatory properties in vitro and in vivo by inhibiting the macrophage M1 polarization and protecting intestinal barrier function.Mech-anistically,1,8-cineole directly interacted with HSP90 and decreased its ATPase activity,also inhibited nucleotide-binding and oligomerization domain-,leucine rich repeat-,and pyrin domain-containing 3(NLRP3)binding to HSP90 and suppressor of G-two allele of SKP1(SGT1)and suppressed NLRP3 inflammasome activation in macrophages.These results demonstrated that 1,8-cineole is a potential drug candidate for UC treatment.
