1,8-cineole ameliorates colon injury by downregulating macrophage M1 polarization via inhibiting the HSP90-NLRP3-SGT1 complex

Shengsuo Ma; Bing Yang; Yang Du; Yiwen Lv; Jiarong Liu; Yucong Shi; Ting Huang; Huachong Xu; Li Deng; Xiaoyin Chen

doi:10.1016/j.jpha.2023.07.001

Volume 13 Issue 9

Sep. 2023

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Article Navigation > Journal of Pharmaceutical Analysis > 2023 > 13(9): 984-998

Shengsuo Ma, Bing Yang, Yang Du, Yiwen Lv, Jiarong Liu, Yucong Shi, Ting Huang, Huachong Xu, Li Deng, Xiaoyin Chen. 1,8-cineole ameliorates colon injury by downregulating macrophage M1 polarization via inhibiting the HSP90-NLRP3-SGT1 complex[J]. Journal of Pharmaceutical Analysis, 2023, 13(9): 984-998. doi: 10.1016/j.jpha.2023.07.001

Citation:

Shengsuo Ma, Bing Yang, Yang Du, Yiwen Lv, Jiarong Liu, Yucong Shi, Ting Huang, Huachong Xu, Li Deng, Xiaoyin Chen. 1,8-cineole ameliorates colon injury by downregulating macrophage M1 polarization via inhibiting the HSP90-NLRP3-SGT1 complex[J]. Journal of Pharmaceutical Analysis, 2023, 13(9): 984-998. doi: 10.1016/j.jpha.2023.07.001

Citation:

Shengsuo Ma, Bing Yang, Yang Du, Yiwen Lv, Jiarong Liu, Yucong Shi, Ting Huang, Huachong Xu, Li Deng, Xiaoyin Chen. 1,8-cineole ameliorates colon injury by downregulating macrophage M1 polarization via inhibiting the HSP90-NLRP3-SGT1 complex[J]. Journal of Pharmaceutical Analysis, 2023, 13(9): 984-998. doi: 10.1016/j.jpha.2023.07.001

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1,8-cineole ameliorates colon injury by downregulating macrophage M1 polarization via inhibiting the HSP90-NLRP3-SGT1 complex

doi: 10.1016/j.jpha.2023.07.001

Shengsuo Ma^a,b,
Bing Yang^a,b,
Yang Du^a,b,
Yiwen Lv^a,b,
Jiarong Liu^a,b,
Yucong Shi^a,
Ting Huang^a,
Huachong Xu^{a,b
,
,},
Li Deng^{a,b
,
,},
Xiaoyin Chen^{a
,
,}

a. School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China;
b. Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China

Funds:

This work was supported by the National Natural Science Foundation of China (Grant Nos.: 81830114, 82004232, 82174253, and 82104707), Guangdong Basic and Applied Basic Research Foundation, China (Grant Nos.: 2021A1515011215 and 2022A1515110827), Guangzhou Basic and Applied Basic Research Foundation, China (Grant No.: 2023A1515011149), China Postdoctoral Science Foundation (Grant Nos.: 2020M683206 and 2021M701443), the Key Area Research and Development Program of Guangdong Province, China (Grant No.: 2020B1111100010), Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, China (Grant No.: 202102010014), the Cross-disciplinary Special Project of Jinan University, China (Grant No.: 21621115), the State Key Laboratory of Dampness Syndrome of Chinese Medicine, China (Grant No.: SZ2021KF13), and the Outstanding Innovative Talents Cultivation Funded Programs for Doctoral Students of Jinan University, China (Grant No.: 2021CXB024).

Received Date: Feb. 18, 2023
Accepted Date: Jul. 01, 2023
Rev Recd Date: Jun. 08, 2023
Publish Date: Jul. 06, 2023

Abstract

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 treatment 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 sodium 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. Mechanistically, 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.
- 1,8-cineole,
- Amomum compactum Sol. ex Maton,
- NLRP3,
- HSP90,
- Ulcerative colitis,
- Intestinal barrier function

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References(33)

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