Rosmarinic acid ameliorates septic-associated mortality and lung injury in mice via GRP78/IRE1α/JNK pathway. (16th March 2021)

• Record Type: Journal Article
• Authors: Zhang, Zheng-kun; Zhou, Yan; Cao, Jun; Liu, Dan-yang; Wan, Li-hong
• Is Part Of: Journal of pharmacy and pharmacology. Volume 73:Number 7(2021)
• Page Start: 916
• Page End: 921
• Publication Date: 2021-03-16
• Subjects: rosmarinic acid (RA) -- septic-associated lung injury -- oxidative stress -- ER stress related apoptosis -- GRP78/IRE1α/JNK pathway; Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1093/jpp/rgaa033
• Languages: English
• ISSNs: 0022-3573

Abstract

Abstract: Objectives: Acute lung injury (ALI) is the major complication of sepsis, and no effective treatment is available now. Recently, rosmarinic acid (RA), a water-soluble polyphenolic phytochemical, exerts a potential role on ALI with anti-inflammation, and antioxidant properties. However, there is still no evidence on its protective effect on cell apoptosis in sepsis. Here, we investigated the protective effect of RA in septic-associated mortality and lung injury based on apoptosis. Methods: Male C57BL/6 mice were administered with lipopolysaccharide (LPS) (15 mg/kg, ip) to establish ALI mice model. Preteatment of RA (20 or 40 mg/kg, ip) was performed once daily for five consecutive days. The mortality was monitored for seven days after injection of LPS. Key findings: RA (40 mg/kg) significantly decreased mortality and alleviated septic-associated lung injury. Meanwhile, RA significantly reversed LPS induced decrease in serum T-aoc level and superoxide dismutase (SOD) activity, and increase in malondialdehyde (MDA) activity. Furthermore, RA pretreatment significantly inhibited lung cell apoptosis, as well as decreased p53 level in sepsis mice. Finally, the LPS induced activation of GRP78/IRE1α/JNK pathway was suppressed by RA pretreatment. Conclusions: These findings indicated that RA could be beneficial to septic-associated lung injury through anti-apoptosis effect.