Search

Sepsis triggers liver dysfunction with high morbidity and mortality. Here, we elucidated the effect of anemoside B4 on sepsis in cecal ligation and puncture (CLP)-induced mouse model and LPS-induced primary hepatocytes. Following CLP surgery, septic mice were intraperitoneally injected with anemoside B4 (50 or 100 mg/kg). Anemoside B4 improved septic mouse survival rate, decreased serum AST and ALT levels and attenuated liver histopathologic damages. Western blot analysis showed that anemoside B4 elevated the expression of Beclin-1, LC3II/LC3I, Atg3, Atg5, and Atg7, and reduced p62, suggesting the restoration of autophagy flux in liver. More autophagic vesicles were observed in liver after anemoside B4 treatment using transmission electron microscopy. Using ELISA and commercial enzyme kits, we found that anemoside B4 decreased serum TNF-α, IL-6, and IL-1β levels and increased CAT, SOD and GSH activities. TUNEL staining and western blot revealed that anemoside B4 suppressed cell apoptosis, along with decreased Bax, leaved caspase-3, cleaved PARP, but increased Bcl-2. Consistent with in vivo findings, anemoside B4 inhibited apoptosis, inflammatory response, and oxidative stress and enhanced autophagy in LPS-induced primary hepatocytes. Importantly, these cellular processes were possibly mediated by mTOR/p70S6K signaling, as reflected by the offset of 3-MA in the immunosuppression of anemoside B4. [Display omitted] • Anemoside B4 restored the sepsis-induced impaired autophagy flux. • Anemoside B4 alleviated inflammatory response, oxidative stress and apoptosis in sepsis. • The hepatoprotective effect of anemoside B4 might be mediated by the mTOR/p70S6K signaling pathway. [ABSTRACT FROM AUTHOR]

• Blood-brain barrier plays a central role in a variety of central nervous system diseases and is a drug target. • Mitochondrial oxidative stress disorder in brain microvascular endothelial cells plays a key role in the occurrence and development of blood–brain barrier damage. • Protection of mitochondrial function in brain microvascular endothelial cells is a potential new strategy for the treatment of central nervous system diseases. Blood-brain barrier disruption plays an important role in central nervous system diseases. This review provides information on the role of mitochondrial oxidative stress in brain microvascular endothelial cells in cellular dysfunction, the disruption of intercellular junctions, transporter dysfunction, abnormal angiogenesis, neurovascular decoupling, and the involvement and aggravation of vascular inflammation and illustrates related molecular mechanisms. In addition, recent drug and nondrug therapies targeting cerebral vascular endothelial cell mitochondria to repair the blood–brain barrier are discussed. This review shows that mitochondrial oxidative stress disorder in brain microvascular endothelial cells plays a key role in the occurrence and development of blood–brain barrier damage and may be critical in various pathological mechanisms of blood–brain barrier damage. These new findings suggest a potential new strategy for the treatment of central nervous system diseases through mitochondrial modulation of cerebral vascular endothelial cells. [ABSTRACT FROM AUTHOR]