Phycocyanin Ameliorates Radiation‐Induced Acute Intestinal Toxicity by Regulating the Effect of the Gut Microbiota on the TLR4/Myd88/NF‐κB Pathway

Abstract

Background Radiation‐induced gastrointestinal syndrome, including nausea, diarrhea, and dehydration, contributes to morbidity and mortality after medical or industrial radiation exposure, which seriously affects patient quality of life after treatment. No safe and effective radiation countermeasure has been approved for clinical therapy. In this study, we aimed to investigate the potential protective effects of phycocyanin (PC) against radiation‐induced acute intestinal injury. Materials and Methods C57BL/6 mice were orally administered 50 mg/kg PC once per day for 1 month before exposure to total‐abdominal x‐ray irradiation at a single dose of 12 Gy. The effects of PC on intestinal histopathology and integrity, gut microbiota, lipopolysaccharides (LPS), inflammatory cytokines, and Toll‐like receptor 4 (TLR4)/myeloid differentiation factor 88 (Myd88)/nuclear factor κB (NF‐κB) signaling were evaluated. Results Severe histopathological damage, such as intestinal mucosal epithelial cell apoptosis, necrosis, and nuclear rupture, was most clearly observed 24 hours after total‐abdominal x‐ray irradiation. Intestinal integrity was damaged by irradiation, which manifested in reduced levels of the tight‐junction proteins Claudin‐1, Occludin, and zonula occludens‐1(ZO‐1). PC pretreatment significantly ameliorated radiation‐induced intestinal injury. PC also modulated the gut microbiota composition, increasing the proportion of beneficial bacteria and decreasing that of harmful bacteria, which in turn lowered LPS levels and suppressed TLR4/Myd88/NF‐κB pathway activation. Finally, levels of corresponding inflammatory cytokines, including tumor necrosis factor α and interleukin‐6, were also downregulated. Conclusion PC protects against mouse intestinal injury from high‐dose radiation by regulating the effect of the gut microbiota on the TLR4/Myd88/NF‐κB pathway, suggesting PC as a promising natural radiation countermeasure.

Effects of phycocyanin on pulmonary and gut microbiota in a radiation-induced pulmonary fibrosis model

“…Wash the lungs of the mice with 0.5 mL of phosphate buffer. The lavage fluid is then collected and used for genetic testing [ 12 , 14 ]. The extraction of total DNA and the evaluation of bacterial diversity used PowerSoil DNA isolation kit (MoBio Laboratories, Carlsbad, USA, California) and Illumina Hiseq platform.…”

“…It has been reported that PC can alleviate paraquat-induced lung injury in rats [ 8 ]. Research found that in the bleomycin-induced mouse lung fibrosis model, PC could regulate TLR2-MyD88-NF-κB signaling pathways alleviate pulmonary fibrosis [ 9 ], and in addition, could significantly reduce bacteria that associated with inflammation, thereby alleviating pulmonary fibrosis [ [10] , [11] , [12] ].…”

Gut Microbiota Metabolite Fights Against Dietary Polysorbate 80-Aggravated Radiation Enteritis

“…Specifically, it has been reported in our previously studies that TAI had no effect on the abundance of the intestinal bacterial of mice after 3 days (Cui et al, 2017a), 5 days (Xiao et al, 2018) and 6 or 12 days (Li et al, 2020) of TAI. In addition, recently study reported that after 1 month of TAI, there was no significant change in the abundance of gut microbiota (Lu et al, 2019). All the studies prove that TAI unchanges the α-diversity of gut microbiota in hosts.…”

Combined Lycium barbarum polysaccharides and C-phycocyanin increase gastric Bifidobacterium relative abundance and protect against gastric ulcer caused by aspirin in rats

“…Our data indicated that CPC (a bioactive ingredient of spirulina) treatment significantly increased the class Actinobacteria , the order Bifidobacteriales , the family Bifidobacteriaceae , and the genus Bifidobacterium in the stomach. A recent study showed that daily oral pretreatment of phycocyanin (50 mg/kg bw) for 30 days increased the proportion of beneficial bacteria such as the genera Lactobacillus , Bifidobacterium , and Roseburia and decreased that of harmful bacteria such as the genus Desulfovibrio in the phylum Proteobacteria in the cecum and feces of mice with radiation-induced acute gastrointestinal syndrome [ 20 ]. The pretreatment of phycocyanin improved ileal integrity via increasing tight junction proteins and decreased intestinal inflammatory signaling proteins in mice with radiation-induced acute gastrointestinal syndrome [ 20 ].…”

“…C-phycocyanin has been found to possess hepatoprotective, antioxidant, anti-inflammatory, and wound healing properties [ 16 – 18 ]. Due to the characteristics of free oxygen radical scavenger, anti-inflammatory, immunomodulatory, regenerative, and wound-healing activities for LBP and CPC, it is reasonably hypothesized that LBP and/or CPC may exert the recovery of gastric ulcer through lowering oxidative damage, inhibiting pro-inflammatory responses, improving gastroprotection, and altering gastric microbiota [ 13 – 20 ]. The aim of this study was to investigate whether Lycium barbarum polysaccharides and/or C-phycocyanin could have healing potential on gastric ulcer caused by aspirin in rats.…”