Ginkgolic acid promotes inflammation and macrophage apoptosis via SUMOylation and NF-κB pathways in sepsis

Xinyong Liu; Longwang Chen; Chen Zhang; Wei Dong; Hongbing Liu; Zhong Xiao; Kang Wang; Yaolu Zhang; Yahui Tang; Guangliang Hong; Zhongqiu Lu; Guangju Zhao

doi:10.3389/fmed.2022.1108882

Ginkgolic acid promotes inflammation and macrophage apoptosis via SUMOylation and NF-κB pathways in sepsis

Front Med (Lausanne). 2023 Jan 19:9:1108882. doi: 10.3389/fmed.2022.1108882. eCollection 2022.

Authors

Xinyong Liu^{1

2}, Longwang Chen^{1

2}, Chen Zhang^{1

2}, Wei Dong^{1

2}, Hongbing Liu^{1

2}, Zhong Xiao^{1

2}, Kang Wang^{1

2}, Yaolu Zhang^{1

2}, Yahui Tang^{1

2}, Guangliang Hong^{1

2}, Zhongqiu Lu^{1

2}, Guangju Zhao^{1

2}

Affiliations

¹ Department of Emergency Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
² Wenzhou Key Laboratory of Emergency and Disaster Medicine, Wenzhou, China.

Abstract

Background: Excessive inflammation and increased apoptosis of macrophages contribute to organ damage and poor prognosis of sepsis. Ginkgolic acid (GA) is a natural constituent extracted from the leaves of Ginkgo biloba, that can regulate inflammation and apoptosis. The present study aims to investigate the potential effect of GA in treating sepsis and its possible mechanisms.

Materials and methods: Here, a classic septic mice model and a lipopolysaccharide (LPS)-induced RAW 264.7 inflammation model were established. Cytokines in serum and culture supernatant were detected by ELISA, and the mRNA levels of them were examined by PCR. Hematoxylin and eosin (H&E) staining was performed to determine histopathological changes in liver, lung and kidney. Bacterial burden in the blood, peritoneal lavage fluids (PLFs) and organs were observed on Luria-Bertani agar medium. Flow cytometry and western blotting was used to detect apoptosis and the expression level of apoptosis related molecules, respectively. Moreover, the levels of SUMOylation were detected by western blotting. The activity of NF-κB p65 was assessed by immunofluorescence staining and western blotting.

Results: The result showed that GA promoted inflammatory responses, reduced bacterial clearance, aggravated organ damage, and increased mortality in septic mice. GA increased apoptosis in peritoneal macrophages (PMs) and RAW 264.7 cells. Meanwhile, GA inhibited SUMOylation and increased the nuclear translocation of NF-κB p65 as well as its phosphorylation level.

Conclusion: Collectively, GA promotes inflammation and macrophage apoptosis in sepsis, which may be mediated by inhibiting the SUMOylation process and increasing NF-κB p65 activity.

Keywords: NF-κB; SUMO; ginkgolic acid; inflammation; macrophage; sepsis.

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 81871583), Natural Science Foundation of Zhejiang Province (No. LQ22H150003), Key R&D Program Projects of Zhejiang Province (No. 2021C03072), National Key R&D Program of China (No. 2018YFC2000305), the Key Specialty of Traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan Period (Emergency Department), and Zhejiang Provincial Innovative Team for The Diagnosis and Treatment of Sepsis with Integrated Traditional Chinese and Western Medicine.