Nicaraven protects against endotoxemia-induced inflammation and organ injury through modulation of AMPK/Sirt1 signaling in macrophages

Zha, Duoduo; Yang, Yunjuan; Huang, Xiang; Wang, Ziwei; Lin, Hong‐Ru; Yang, Lingyi; Xu, Liang; Wu, Yijia; Huang, Houda; Wang, Yihan; Xin, Zhaochen; Wu, Xuehan; Yan, Xiao; Li, Tao‐Sheng; Deng, Ke-Yu; Xin, Hong‐Bo; Qian, Yisong

doi:10.1016/j.ejphar.2023.175666

Cited by 4 publications

(1 citation statement)

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“…Once stimulated appropriately, macrophages can polarize into two phenotypes: M1 macrophages, which primarily engage in anti-infection and pro-inflammatory reactions; and M2 macrophages, which play significant roles in suppressing inflammation and facilitating tissue repair ( 53 ). SIRT1 is capable of regulating monocyte functions through NF-κB and the peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1), promoting the expression and activation of SIRT1 in macrophages, leading to a downregulation of M1 polarization markers such as TLR4, p-NF-κB, IL-1β, and iNOS, while upregulating M2 polarization markers like Arg1, thus facilitating the polarization towards M2 macrophages and mitigating the inflammatory response ( 54 , 55 ). In addition to influencing macrophage immune phenotypes, Sirt1 binds to deacetylated lysine residues (28-30) of HMGB1, forming a stable nuclear complex and inhibiting its release.…”

Section: Sirts and Pathophysiology Of Sepsismentioning

confidence: 99%

The role and therapeutic potential of SIRTs in sepsis

You,

Li,

Chong

2024

Front. Immunol.

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Sepsis is a life-threatening organ dysfunction caused by the host’s dysfunctional response to infection. Abnormal activation of the immune system and disturbance of energy metabolism play a key role in the development of sepsis. In recent years, the Sirtuins (SIRTs) family has been found to play an important role in the pathogenesis of sepsis. SIRTs, as a class of histone deacetylases (HDACs), are widely involved in cellular inflammation regulation, energy metabolism and oxidative stress. The effects of SIRTs on immune cells are mainly reflected in the regulation of inflammatory pathways. This regulation helps balance the inflammatory response and may lessen cell damage and organ dysfunction in sepsis. In terms of energy metabolism, SIRTs can play a role in immunophenotypic transformation by regulating cell metabolism, improve mitochondrial function, increase energy production, and maintain cell energy balance. SIRTs also regulate the production of reactive oxygen species (ROS), protecting cells from oxidative stress damage by activating antioxidant defense pathways and maintaining a balance between oxidants and reducing agents. Current studies have shown that several potential drugs, such as Resveratrol and melatonin, can enhance the activity of SIRT. It can help to reduce inflammatory response, improve energy metabolism and reduce oxidative stress, showing potential clinical application prospects for the treatment of sepsis. This review focuses on the regulation of SIRT on inflammatory response, energy metabolism and oxidative stress of immune cells, as well as its important influence on multiple organ dysfunction in sepsis, and discusses and summarizes the effects of related drugs and compounds on reducing multiple organ damage in sepsis through the pathway involving SIRTs. SIRTs may become a new target for the treatment of sepsis and its resulting organ dysfunction, providing new ideas and possibilities for the treatment of this life-threatening disease.

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Section: Sirts and Pathophysiology Of Sepsismentioning

confidence: 99%