The Therapeutic Effect and the Possible Mechanism of C-Phycocyanin in Lipopolysaccharide and Seawater-Induced Acute Lung Injury

Leifang Zhang; Deyi Kong; Junxia Huang; Qiongfen Wang; Lilin Shao

doi:10.2147/DDDT.S347772

The Therapeutic Effect and the Possible Mechanism of C-Phycocyanin in Lipopolysaccharide and Seawater-Induced Acute Lung Injury

Drug Des Devel Ther. 2022 Apr 6:16:1025-1040. doi: 10.2147/DDDT.S347772. eCollection 2022.

Authors

Leifang Zhang¹, Deyi Kong¹, Junxia Huang¹, Qiongfen Wang², Lilin Shao¹

Affiliations

¹ Zhejiang Provincial Engineering Technology Research Center of Marine Biomedical Products, School of Food and Pharmacy, Zhejiang Ocean University, Zhoushan, 316022, People's Republic of China.
² Zhoushan Institute of Calibration and Testing for Quality and Technical Supervision, Zhoushan, 316012, Zhejiang, People's Republic of China.

Abstract

Background: Seawater drowning-induced acute lung injury (ALI) is a severe clinical condition characterized by increased alveolar-capillary permeability, excessive inflammatory response, and refractory hypoxemia. C-phycocyanin (C-PC), a biliprotein found in blue-green algae such as spirulina platensis, is widely used in the food and dietary nutritional supplement fields due to its beneficial pharmacological effects. Previous studies have revealed that C-PC has anti-inflammatory, antioxidant, and anti-apoptotic activities.

Purpose: Therefore, this study investigated the protective effect and underlying mechanisms of C-PC on lipopolysaccharide (LPS) and seawater (SW) induced ALI (SW and LPS-induced ALI).

Methods: An SW and LPS mouse model of ALI mice was established through intratracheal administration of 5mg/kg LPS and 25% SW. Different doses of C-PC (100, 200 and 400 mg/kg) were administered by intraperitoneal injection for seven days. In addition, gap junction communication in RAW264.7 and MLE-12 cells was determined following stimulation with 25% SW and 10 μg/ml LPS after treatment with C-PC (120 μg/ml). Moreover, the arterial partial pressure of oxygen, lung wet/dry weight ratios, total protein content and MPO levels in the bronchoalveolar lavage fluid (BALF), and the histopathologic and ultrastructure staining of the lung tissues were determined. The oxidative stress index, levels of the pro-inflammatory mediators, epithelial cell viability and apoptosis, and the regulatory effect of C-PC on the NF-κB/NLRP3 axis were investigated.

Results: The results showed that C-PC significantly alleviated pathological damages, suppressed oxidative stress, inflammation and apoptosis, and enhanced the viability of epithelial cells in the lung tissues. Furthermore, C-PC was shown to inhibit activation of the NF-κB/NLRP3 pathway and the formation of the NLRP3 inflammasome complex.

Conclusions: In conclusion, C-PC shows promising therapeutic value in SW and LPS-induced ALI/ARDS, providing new insight into ALI/ARDS treatment.

Keywords: C-phycocyanin; NF-κB/NLRP3; acute lung injury; apoptosis; inflammation.

MeSH terms

Acute Lung Injury* / chemically induced
Acute Lung Injury* / drug therapy
Acute Lung Injury* / metabolism
Animals
Lipopolysaccharides
Lung
Mice
NF-kappa B / metabolism
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Phycocyanin* / pharmacology
Respiratory Distress Syndrome*
Seawater / adverse effects

Substances

Lipopolysaccharides
NF-kappa B
NLR Family, Pyrin Domain-Containing 3 Protein
Phycocyanin

Grants and funding

This work received financial support from the National Natural Science Foundation of China (Grant No. 81903693), Fundamental Research Funds for Zhejiang Provincial Universities and Research Institutes (Grant No. 2019J00013), Science and Technology Plan Project of Zhoushan (Grant No. 2020C21018), and the National Undergraduate Training Program for Innovation and Entrepreneurship (Grant No. 201910340019).