Liensinine, a alkaloid from lotus plumule, mitigates lipopolysaccharide-induced sepsis-associated encephalopathy through modulation of nuclear factor erythroid 2-related factor-mediated inflammatory biomarkers and mitochondria apoptosis.
Guanglu WangYong SunQiankun YangDapeng DaiLe ZhangHui FanWei ZhangJingquan DongPanpan ZhaoPublished in: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (2023)
The present study aims to investigate the role of liensinine in life-threatened sepsis-associated encephalopathy (SAE) mice and the underlying mechanism. Here, seventy-two mice were divided into six groups, including the control group, SAE group, liensinine-treated group, and three doses of liensinine-treated SAE groups. Lipopolysaccharide triggered cerebrum necrosis and disrupted the integrity and permeability of blood-brain barrier (BBB). While liensinine restored cerebrum structure and improved BBB integrity with upregulated tight junction proteins, decreased evans blue leakage and fibrinogen expression with decreased matrix metalloproteinases 2/9 in serum, thereby reducing BBB permeability. Moreover, lipopolysaccharide triggered cerebrum oxidative stress and inflammation, whereas liensinine enhanced antioxidant enzymes activities and weakened malondialdehyde through nuclear factor erythroid 2-related factor. Meanwhile, liensinine inhibited inflammation by activating inducible nitric oxide synthase. Tunel staining combined with transmission electron microscope indicated that lipopolysaccharide induced cerebrum apoptosis, whereas liensinine blocked apoptosis through decreasing B-cell lymphoma-2 associated X (Bax) expression and cytochrome C (Cyto-c) release, increasing B-cell lymphoma-2 (Bcl-2) expression, blocking apoptosome assembly, inhibiting caspase-3 activation, thereby suppressing intrinsic mitochondria apoptosis. Recovering of inflammatory homeostasis and inhibition of mitochondria apoptosis by liensinine ultimately restored cognitive function in SAE mice. Altogether, liensinine attenuated lipopolysaccharide-induced SAE via modulation of Nrf2-mediated inflammatory biomarkers and mitochondria apoptosis.
Keyphrases
- oxidative stress
- lipopolysaccharide induced
- blood brain barrier
- inflammatory response
- nuclear factor
- cell death
- toll like receptor
- induced apoptosis
- cell cycle arrest
- ischemia reperfusion injury
- diabetic rats
- dna damage
- endoplasmic reticulum stress
- poor prognosis
- lps induced
- signaling pathway
- nitric oxide synthase
- intensive care unit
- nitric oxide
- acute kidney injury
- reactive oxygen species
- metabolic syndrome
- immune response
- adipose tissue
- skeletal muscle
- drug induced
- cerebral ischemia
- heat shock protein
- septic shock