Crocetin Improves Dengue Virus-Induced Liver Injury

Abstract

Dengue virus (DENV) infection is one of the most widespread mosquito-borne viral infections. Liver injury is commonly observed in severe DENV infection, and the present study aimed to examine the efficacy of crocetin treatment in an immunocompetent mouse model of DENV infection exhibiting liver injury. The efficacy of crocetin treatment in DENV-induced liver injury was assessed via both transaminase levels and histopathology analysis. A real-time polymerase chain reaction array was then used to describe the expression of 84 apoptosis-related genes. Using real-time RT-PCR and Western blot analysis, the gene expressions of host factors were investigated. Additionally, the effect of crocetin in NF-kB signaling during DENV infection was studied. We did not observe any significant reduction in virus production when DENV-infected mice were treated with crocetin. However, DENV-infected mice treated with crocetin showed reduced DENV-induced apoptosis. The real-time polymerase chain reaction array revealed pro-inflammatory cytokine expressions to be significantly reduced in the crocetin-treated DENV-infected mice. We also found that crocetin could effectively modulate antioxidant status in DENV-infected mice. Moreover, crocetin demonstrated the ability to reduce the nuclear translocation of NF-kB in DENV-infected mice. Our results suggest that crocetin treatment does not inhibit DENV replication in the liver of DENV-infected mice; however, we did find that crocetin improves host responses that reduce liver injury.

Crocetin Protected Human Hepatocyte LO2 Cell From TGF-β-Induced Oxygen Stress and Apoptosis but Promoted Proliferation and Autophagy via AMPK/m-TOR Pathway

“…Dhar et al ( 23 ) used hemorrhagic shock mice to confirm the protective effect of crocetin on survival and liver tissue damage. Sreekanth et al ( 24 ) found that crocetin could improve dengue virus-induced liver injury but could not suppress virus replication. As a traditional drug, crocetin is considered to have benefits on the nervous system, protective effects from cardiovascular disease, antioxidation, and so on.…”

Crocetin and related oxygen diffusion‐enhancing compounds: Review of chemical synthesis, pharmacology, clinical development, and novel therapeutic applications

“…In an interesting investigation, 4 was shown to improve Dengue virus (DENV)‐induced liver injury in immunocompetent mouse model of DENV infection with observed liver injury without any significant effect on viral load (Sreekanth et al, 2020 ). Major inhibitory effects were observed on DENV‐induced apoptosis, pro‐inflammatory cytokine expressions and NF‐κB nuclear translocation.…”

Exploring the Protective Effects and Mechanism of Crocetin From Saffron Against NAFLD by Network Pharmacology and Experimental Validation

“…( 42 ). In studies of liver diseases, CCT showed comparative beneficial effects on CCL 4 -induced and dengue virus-induced liver damage via induction of antioxidant defense ( 43 , 44 ). In this study, the therapeutic targets of crocin I, crocin II, and CCT were combined, because orally administered crocins are hydrolyzed to CCT before they are incorporated into the blood circulation, and these findings have been confirmed in several pharmacokinetic studies ( 45 – 47 ).…”