Protective Effects of Bee Venom-Derived Phospholipase A2 against Cholestatic Liver Disease in Mice

Abstract

Hepatocyte apoptosis and inflammation play important roles in cholestatic liver diseases. Bee venom-derived secretory phospholipase A2 (bvPLA2) has been shown to ameliorate various inflammatory diseases. However, whether bvPLA2 has a therapeutic effect against cholestatic liver disease has not been evaluated. Therefore, we investigated the effects of bvPLA2 on cholestatic liver injury and fibrosis in a murine model of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet feeding. The administration of bvPLA2 ameliorated liver damage, cholestasis, and fibrosis in DDC diet-fed mice, as assessed by serum biochemical tests and histological examinations. In addition, bvPLA2 reduced myofibroblast accumulation, concomitant with suppression of transforming growth factor-β signaling cascade. The administration of bvPLA2 inhibited hepatocyte apoptosis in DDC diet-fed mice as represented by a reduction in the number of cells stained with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and suppression of caspase-3 activation. Moreover, bvPLA2 reduced cytokine production along with the inhibition of the nuclear factor kappa-B pathway. The number of regulatory T-cells was increased by bvPLA2, while the number of other immune cells, including neutrophils, macrophages, and CD8+ T-cells, was decreased. Our data indicate that the administration of bvPLA2 ameliorates cholestatic liver injury and fibrosis by inhibiting hepatocyte apoptosis and inflammation.

Hispidulin Ameliorates Endotoxin-Induced Acute Kidney Injury in Mice

“…IHC staining with an antibody against F4/80, a macrophage marker [ 33 ], also revealed that LPS injection increased the number of F4/80-positive cells in kidney tissues, which was significantly alleviated by hispidulin administration (LPS, 7.8 ± 1.3 vs. LPS + His, 2.4 ± 0.5, p < 0.001; Figure 8 A,B).…”

“…While Ly6B.2 is expressed mainly on neutrophils, F4/80 is found primarily on macrophages. The infiltration of Ly6B.2-positive or F4/80-positive cells into the damaged tissue has been shown to be increased in various inflammatory diseases, such as postoperative ileus [ 32 ], cisplatin-induced renal injury [ 28 , 31 ], cholestatic liver disease [ 33 , 37 ], nonalcoholic fatty liver disease [ 44 ], and atherosclerosis [ 45 ]. Neutrophils and macrophages may exacerbate the LPS-induced inflammatory responses [ 2 ].…”

Protective Effects of Carnosic Acid on Lipopolysaccharide-Induced Acute Kidney Injury in Mice

“…Furthermore, phosphorylated forms of nuclear factor-κB (NF-κB) p65 and signal transducer and activator of transcription 3 (STAT3) were increased after LPS injection, which was inhibited by carnosic acid (p < 0.05; Figure 4C-E). Neutrophil infiltration was evaluated by detecting cells stained with Ly6B.2, a neutrophil marker [22]. The number of Ly6B.2-positive cells was higher in the LPS group than in the control group (Figure 5A,B).…”

Pharmacological properties and therapeutic potential of honey bee venom

“…Investigators reported that BV group III sPLA 2 can stop the inflammation and death of nerve cells caused by prion protein fragment 106-126 ( Hossen et al, 2017a , Hossen et al, 2017b ). New research show that the treatment with phospholipase A2 significantly cured cholestatic liver injury in mice via the obstruction of inflammation and liver cell apoptosis ( Kim et al, 2021 ). The BV constituent called MCD peptide is composed of 22 amino acids having 2 disulfide bridges and possesses anti - inflammatory potential ( Bellik, 2015 , Komi et al, 2018 ).…”