TABLE 1.

Evidence for sepsis treatment strategies by targeting NLRP3, ROS, autophagy, and mitochondria.

Target point	Compound	Function or mechanism	References
NLRP3 inhibitors	MCC950	MCC950 inhibits NLRP3 inflammasomes to reduce septic death in mice.	Kang et al., 2016; Lin et al., 2019
	Baicalin	Baicalin decreases NLRP3 inflammasome activation to improve survival in sepsis mice by augmenting protein kinase A signaling.	Li C. G. et al., 2017
	Cortistatin	Cortistatin deactivates NLRP3 inflammasome activity to reduce myocardial injury induced by sepsis.	Zhang B. et al., 2015
	Sulfur dioxide	Sulfur dioxide attenuates sepsis-induced cardiac dysfunction by inhibiting inflammation via the TLR4/NLRP3 signaling pathway.	Yang et al., 2018
ROS scavengers	Glutathione	Glutathione exhibits a protective effect by removing excess reactive oxygen species (ROS) in sepsis mice.	Pompella et al., 2003; Zhou et al., 2016; Yang et al., 2019a
	Mitoquinone	Mitoquinone reduces ROS formation to increase the survival rate of mice challenged by LPS.	Lowes et al., 2008; Ramsey and Wu, 2014
Antioxidants (clinical trial)	N-acetylcysteine	N-acetylcysteine improves liver function, respiratory function, and reduces ICU therapy stays for sepsis patients.	Spapen et al., 1998; Rank et al., 2000; Paterson et al., 2003
	Vitamin C	Vitamin C reduces sequential organ failure assessment score, C-reactive protein and procalcitonin, and prevents colistin associated acute kidney injury.	FowlerIII, Syed et al., 2014; Dalfino et al., 2015;
	Selenium	Selenium reduces inflammation biomarkers, and predicts and decreases infection-related hospital mortality.	Forceville, 2007; Valenta et al., 2011; Costa et al., 2014
	Coenzyme Q10	Coenzyme Q10 reduces inflammatory biomarkers and improves survival of sepsis patients.	Soltani et al., 2020
Autophagy activators	Sestrin 2	Sestrin 2 induces mitophagy to clean damaged mitochondria and inhibit NLRP3 activation in sepsis.	Kim et al., 2016a
	Beclin 1 peptide	Beclin-1 protects mitochondria to reduce the release of mitochondrial danger-associated molecular patterns, and promotes mitophagy to decrease sepsis.	Sun et al., 2018
Mitochondrial protectants	Fangjifuling	Fangjifuling suppresses mitochondrial-mediated apoptosis by regulating the Bax/Bcl-2 ratio in LPS-induced inflammatory.	Su et al., 2018
	Resveratrol	Resveratrol attenuates widespread swollen mitochondria with ruptured outer membranes to reverse sepsis-induced myocardial remodeling.	Smeding et al., 2012

NLRP3, NOD-, LRR-, and pyrin domain-containing protein 3; TLR4, Toll-like Receptor 4; Bax/Bcl-2, Bax (apoptosis inducer), Bcl-2 (apoptosis suppressor); LPS, lipopolysaccharides.